The SLCO1B1 NM_006446.5:c.521T>C (NP_006437.3:p.(Val174Ala)) missense variant has previously been reported in somatic cancers (COSMIC; COSV57010105, n = 18 times). Based on available guidelines, this variant is considered to be Benign. This variant is considered to be drug response by the VCEP (ClinPGx; ClinVar ID 37346).
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.SLCO1B1 encodes a liver membrane transporter that helps move bilirubin, steroid conjugates, leukotrienes, and medicines such as statins from the blood into liver cells. Genetic differences can reduce transporter activity and alter how the body handles these compounds, particularly certain medications. SLCO1B1 is not known to have a primary role in cancer.
The recorded framework is Generic ACMG/AMP 2015 with ClinGen SVI recommendations. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
The applied criteria and their strengths are shown as assessed under the stated framework.
No pathogenic criterion marked as applied in the recorded assessment.
Met: gnomAD v4.1 grpmax FAF is 0.195837, exceeding the BA1 threshold of 0.05 in a population with 63,968 observed alleles.
Met: gnomAD v4.1 grpmax FAF is 0.195837, far above the generic BS1 threshold of 0.01 with 63,968 Finnish observed alleles.
Met, supporting: REVEL 0.221 is at or below the <=0.29 generic BP4 supporting threshold for missense variants.
Benign: BA1 stand-alone benign is met by the high population frequency, with additional BS1 (strong) and BP4 (supporting) evidence.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 228,311 / 1,604,544 alleles. Recorded AF 0.14229. Recorded homozygote count 17896.
This variant is present in gnomAD v2.1 (AF= 0.133191; MAF= 13.31914%, 37601/282308 alleles, homozygotes = 2959) and has highest observed frequency in the European (Finnish) population (AF= 0.212418; MAF= 21.24183%, 5330/25092 alleles, homozygotes = 561); grpmax FAF= 0.170731.
This variant is present in gnomAD-Canada v1.0 (AF= 0.1482608695652174, 2728/18400 alleles, homozygotes = 222).
Recorded REVEL score: 0.221. Refer to the recorded PP3/BP4 rationale for interpretation.
7 Benign · 1 Likely benign · 1 other. ClinVar API review status: reviewed by expert panel.
No standalone functional evidence summary is recorded in evidence_summary.functional.
This variant has previously been reported in somatic cancers (COSMIC; COSV57010105, n = 18 times).
This variant does not lie in a statistically significant hotspot.
ACMG/AMP criteria under Generic ACMG/AMP 2015 with ClinGen SVI recommendations, with the data and sources behind each one.
28 criteria with recorded statuses: 3 met · 9 not met · 12 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
No qualifying de novo, segregation, or non-segregation evidence is available for PS2, PM6, PP1, or BS4.
The available studies are pharmacogenetic association cohorts and do not substitute for disease-focused proband, parental, pedigree, or meiosis data.
The exact variant is SLCO1B1 NM_006446.5:c.521T>C (p.Val174Ala), also called rs4149056/SLCO1B1*5.
PS4 was evaluated using the case-control studies already extracted for the exact variant; the strongest reported OR was 4.47, below the governing >5.0 threshold.
PP4 is not met because statin-associated adverse reactions are treatment-related and multifactorial rather than highly specific for a single-gene disease.
PP5 and BP6 do not trigger because the exact-variant expert-panel ClinVar classification is drug response, while benign and likely-benign entries are ordinary laboratory submissions.
BP5 remains not assessed because no alternate molecular basis was established in the available evidence.
This missense variant is adjudicated on the REVEL path only: REVEL 0.221 does not support PP3 but meets generic BP4 at supporting strength.
No criteria match.
BA1 is met. The required filtering frequency is the gnomAD grpmax FAF, not the population point estimate. gnomAD v4.1 reports grpmax FAF=0.19583668, with the maximum-frequency Finnish population represented by 13,336/63,968 observed alleles, well above the minimum 2,000 observed alleles and the generic BA1 threshold of 0.05. gnomAD v2.1 independently reports grpmax FAF=0.17073139 with 5,330/25,092 Finnish alleles. The variant is therefore far above the stand-alone threshold using adequately sized population data; the available case evidence does not document a pathogenic disease consensus or a reduced-penetrance disease association that would warrant withholding BA1.
Allele frequency is above 5% in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium. ... BA1 (stand-alone): >= 0.05 — ACMG/AMP 2015 stand-alone benign allele frequency (PMID:25741868)
BS1 is met under the supplied generic default. The filtering frequency is gnomAD v4.1 grpmax FAF=0.19583668, supported by 63,968 observed alleles in the Finnish subgroup, and gnomAD v2.1 independently gives grpmax FAF=0.17073139 with 25,092 Finnish alleles. Both are far above the generic BS1 default of 0.01. The available case evidence does not identify a disease prevalence, penetrance, allelic-heterogeneity model, or documented founder/reduced-penetrance disease association that would justify overriding this generic frequency assessment.
Allele frequency is greater than expected for the disorder. ... BS1 (strong): >= 0.01 — Generic SVI default; per-gene derivation preferred (Whiffin et al. 2017) (PMID:28518168)
The variant is a missense SNV, p.(Val174Ala), so the generic missense path applies and REVEL is the sole permitted predictor path for PP3/BP4. REVEL is 0.221, which is at or below the generic BP4 supporting threshold of <= 0.29; the SpliceAI result and BayesDel score are not used for this missense criterion. BP4 is met at supporting strength.
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc)
The variant is NP_006437.3:p.(Val174Ala), but the available records establish it as a pharmacogenomic/drug-response allele rather than as a previously established pathogenic variant. ClinVar lists an expert-panel drug-response classification and benign/likely-benign laboratory submissions; no previously established pathogenic same-amino-acid record was identified. The cited papers report statin pharmacokinetic or toxicity associations, not an ACMG pathogenic classification for the same amino-acid change.
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change. ... Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
PS4 is applicable because multiple studies directly evaluated exact variant rs4149056/SLCO1B1 c.521T>C in affected statin-myopathy or adverse-reaction cases and comparison participants. The literature includes case-control comparisons: PMID:28940218 reported C-allele carriage 37.6% in 125 cases versus 25.8% in 481 controls, OR 1.73 (95% CI 1.14-2.62); PMID:26086347 reported 521TC/CC genotypes in 55.3% of 60 adverse-reaction cases versus 44.7% of 90 matched controls, adjusted OR 2.26 (95% CI 1.03-4.98); PMID:23942138 reported OR 2.08 (95% CI 1.35-3.23) for all myopathy and OR 4.47 for severe myopathy; PMID:21243006 reported OR 3.2 (95% CI 0.83-11.96) among simvastatin users; and PMID:27595674 reported OR 1.40 (95% CI 0.74-2.64). These are valid case-control comparisons even where the paper did not provide an odds ratio initially; the reported counts and frequencies were evaluated as case-control evidence. The governing PS4 threshold is OR >5.0 with a confidence interval excluding 1.0. The decisive explicit comparison is 4.47 > 5.0? no; the strongest reported OR does not reach the required threshold, and the other reported ORs are also below 5.0. Therefore PS4 is not met. PMID:19833260 was checked in its full-text extraction and reports an association with a composite statin adverse event but not a qualifying OR >5.0 case-control result.
The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls. ... Relative risk (RR) or odds ratio (OR), as obtained from case-control studies, is >5.0 and the confidence interval around the estimate of RR or OR does not include 1.0.
The variant lies at residue 174. No VCEP-specific domain table is present for SLCO1B1, and the generic evidence bundle provides no established critical functional domain or mutational-hotspot designation for residue 174. The cancerhotspots.org query for SLCO1B1 V174 returned no statistically significant hotspot, and no VCEP hotspot route applies.
Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.
PM2 is not met. The variant is common in the default all-comers gnomAD datasets: gnomAD v4.1 reports AF=0.142290 with 228,311/1,604,544 alleles and gnomAD v2.1 reports AF=0.133191 with 37,601/282,308 alleles. The non-cancer exome subset also reports AF=0.131422 from 31,072/236,430 alleles. These frequencies are vastly above the supplied PM2 supporting threshold of <=0.0001, so the variant is neither absent nor extremely rare in controls.
Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium. ... PM2 (supporting): <= 0.0001 — SVI recommendation to downgrade PM2 to Supporting (ClinGen SVI 2020) (PMID:25741868)
The gene-level prerequisite of a low rate of benign missense variation is not supported. The queried missense variant itself is a common population allele: gnomAD v4.1 reports AF 0.142290 and 17,896 homozygotes, while gnomAD v2.1 reports AF 0.133191 and 2,959 homozygotes. This substantial benign-population variation is inconsistent with applying PP2, and the supplied evidence does not establish that missense variation is a common disease mechanism for SLCO1B1-related disease.
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
The variant is a missense SNV, p.(Val174Ala), so the generic missense path applies and REVEL is the sole permitted predictor path for PP3/BP4. REVEL is 0.221, below the generic PP3 supporting threshold of >= 0.644; the SpliceAI result and BayesDel score are not used for this missense criterion. The criterion is therefore not met.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.).
The available phenotype evidence concerns statin-induced myopathy, muscle symptoms, or dose-related adverse drug reactions, which are pharmacologic adverse-event phenotypes with recognized environmental and multifactorial contributors rather than a highly specific phenotype for a single-gene disease. The reviewed studies also evaluate multiple candidate genes and treatment exposures. The phenotype therefore does not satisfy the requirement for a phenotype or family history highly specific for a disease with a single genetic etiology.
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
No qualifying exact-variant ClinVar expert-panel classification of pathogenic or likely pathogenic was identified. ClinVar lists the exact variant as drug response with expert-panel review, while the benign and likely-benign submissions summarized in the case evidence are laboratory submissions rather than an expert-panel pathogenic classification. The reviewed literature does not provide a reputable recent pathogenic assertion that is unavailable for independent evaluation; its case-control and pharmacogenetic evidence was independently evaluated for PS4.
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
No qualifying exact-variant ClinVar expert-panel classification of benign or likely benign was identified. The exact ClinVar record is expert-panel reviewed for drug response, not benignity; the Benign and Likely benign classifications in the evidence are ordinary laboratory submissions and are expressly excluded from triggering BP6. No separate reputable-source benign assertion unavailable for independent evaluation was identified.
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
No proband-level disease phenotype, family-history assessment, or confirmed maternity and paternity testing is documented for this variant. The available literature concerns statin pharmacogenetic association cohorts rather than a de novo clinical case, so PS2 cannot be assessed.
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
The available evidence does not establish PS3. Papers report clinical pharmacokinetic or statin-toxicity associations for SLCO1B1 c.521T>C (p.Val174Ala), but the reviewed material does not provide a directly reported, well-established in vitro or in vivo functional assay result with adequate assay controls, biological comparator, and reproducibility information. A paper states that prior transfected-cell transport assays showed reduced OATP1B1 substrate transport, but this is a secondary statement without the primary assay data, quantitative result, controls, or validation details needed to calibrate PS3 strength. Therefore a damaging functional effect cannot be assigned from the available auditable evidence.
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
PM3 cannot be assessed from the available evidence. The case contains no affected-proband observation for a defined recessive disorder involving NM_006446.5:c.521T>C, no pathogenic or likely pathogenic partner variant, and no parental or offspring testing establishing phase. The available literature concerns SLCO1B1 pharmacogenetic drug-response associations rather than a documented compound-heterozygous or biallelic disease observation. Without a confirmed pathogenic allele in trans and phase evidence, the PM3 definition is not satisfied.
For recessive disorders, detected in trans with a pathogenic variant
The available PM5 candidate record contains zero same-residue candidates and explicitly states that classic same-residue PM5 semantics could not be confirmed safely. No independently verified alternate missense substitution at Val174 with a pathogenic determination is available in the supplied evidence.
Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before. ... Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
No clinical de novo observation is documented, and there is no evidence that the variant was absent in either parent. The available literature concerns unrelated statin pharmacogenetic association cohorts rather than an assumed de novo disease case, so PM6 cannot be assessed.
Assumed de novo, but without confirmation of paternity and maternity.
No family pedigree, affected relatives, variant genotypes in relatives, or meioses of co-segregation are documented. The available studies are unrelated pharmacogenetic cohorts and do not establish co-segregation with a disease phenotype in affected family members, so PP1 cannot be assessed.
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease.
BS2 cannot be assessed from the available population data. Homozygotes are observed in gnomAD, including 17,896 in gnomAD v4.1 and 2,959 in gnomAD v2.1, but gnomAD non-cancer status does not establish that individuals were healthy adults, unaffected by a defined disorder, or observed at an age appropriate for a fully penetrant early-onset phenotype. No disease-specific inheritance, penetrance, age-of-onset, or clinically characterized healthy-adult cohort is provided.
BS2
The available evidence does not establish BS3. The reviewed papers contain clinical pharmacokinetic, adverse-event, or myopathy association results and do not provide a well-established in vitro or in vivo study showing no damaging effect on protein function or splicing. The available material therefore cannot support a benign functional conclusion or assign BS3 strength.
Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
No affected family members with available variant genotypes are documented, so there is no evaluable non-segregation result. The available literature does not provide a disease-family pedigree for this variant, and BS4 cannot be assessed.
Lack of segregation in affected members of a family.
The supplied evidence does not establish that SLCO1B1-related disease is caused primarily by truncating variants. The available literature and ClinVar records concern pharmacogenomic effects and drug-response phenotypes, but they do not provide a sufficiently characterized disease-variant spectrum demonstrating a primarily truncating mechanism. BP1 therefore cannot be adjudicated from the available evidence.
Missense variant in a gene for which primarily truncating variants are known to cause disease.
BP2 cannot be assessed from the available evidence. No affected-proband or family-level observation documents NM_006446.5:c.521T>C with a pathogenic variant in trans in a fully penetrant dominant disorder, or with a pathogenic variant in cis under any inheritance pattern. The available exact-variant literature reports pharmacogenetic associations and does not establish cis/trans phase with a pathogenic allele. Therefore, neither BP2 pathway can be applied.
Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
The reviewed evidence documents statin exposure and adverse-event phenotypes but does not establish that this variant was found in a case with an alternate molecular basis for the disease. No qualifying alternate pathogenic molecular diagnosis or explicit alternate molecular basis was available in the phenotype-prevalence evidence.
Variant found in a case with an alternate molecular basis for disease.
PVS1 (ClinGen SVI PVS1 recommendations, PMC6185798, pvs1_generic_framework) applies only to null variant classes — nonsense, frameshift, canonical ±1/2 splice-consensus, translation-initiation-codon loss, and stop-loss variants — each expected to trigger nonsense-mediated decay or otherwise abolish normal protein function. NM_006446.5:c.521T>C in SLCO1B1 is a missense substitution predicted to produce NP_006437.3:p.(Val174Ala). As a result, no null-variant mechanism (nonsense-mediated decay, truncation, or canonical splice disruption) is triggered by this variant class, so PVS1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PVS1 for SLCO1B1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_null_variant_class
PM4 (Richards et al. 2015, PMID:25741868) applies to protein length changes: in-frame insertions/deletions in a non-repetitive region, or stop-loss variants that extend the protein past the reference stop codon. NM_006446.5:c.521T>C in SLCO1B1 is a missense substitution predicted to produce NP_006437.3:p.(Val174Ala). As a result, no change in protein length occurs, so there is nothing for this criterion to evaluate, so PM4's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM4 for SLCO1B1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_stop_loss_or_nonrepeat_indel
BP3 (Richards et al. 2015, PMID:25741868) applies to in-frame insertions/deletions located in a repetitive region without a known function. NM_006446.5:c.521T>C in SLCO1B1 is a missense substitution predicted to produce NP_006437.3:p.(Val174Ala). As a result, the variant does not alter protein length within a repeat region, so there is nothing for this criterion to evaluate, so BP3's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP3 for SLCO1B1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_repeat_region_indel
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_006446.5:c.521T>C in SLCO1B1 is a missense substitution predicted to produce NP_006437.3:p.(Val174Ala). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for SLCO1B1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
Every interpreted variant in SLCO1B1, mapped onto the exon structure of NM_006446.5. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| European (Finnish)13336 / 63,968 | 0.211355 hom |
| Middle Eastern1237 / 6,024 | 0.21143 hom |
| Ashkenazi Jewish5420 / 29,516 | 0.18524 hom |
| European (non-Finnish)178937 / 1,171,366 | 0.1514009 hom |
| Remaining individuals9189 / 62,176 | 0.15727 hom |
| East Asian6142 / 44,750 | 0.14438 hom |
| Admixed American7375 / 59,982 | 0.12481 hom |
| Amish62 / 912 | 0.0681 hom |
| South Asian4282 / 90,926 | 0.047160 hom |
| African/African American2331 / 74,924 | 0.03158 hom |
| European (Finnish)5330 / 25,092 | 0.21561 hom |
| Ashkenazi Jewish1858 / 10,338 | 0.18166 hom |
| Remaining individuals1188 / 7,200 | 0.17110 hom |
| European (non-Finnish)20474 / 128,850 | 0.161663 hom |
| East Asian2500 / 19,938 | 0.13153 hom |
| Admixed American3965 / 35,376 | 0.11234 hom |
| South Asian1542 / 30,552 | 0.0556 hom |
| African/African American744 / 24,962 | 0.0316 hom |
This variant is present in gnomAD v4.1 (AF= 0.14229; MAF= 14.22903%, 228311/1604544 alleles, homozygotes = 17896) and has highest observed frequency in the European (Finnish) population (AF= 0.208479; MAF= 20.84792%, 13336/63968 alleles, homozygotes = 1355); grpmax FAF= 0.195837.
This variant is present in gnomAD v2.1 (AF= 0.133191; MAF= 13.31914%, 37601/282308 alleles, homozygotes = 2959) and has highest observed frequency in the European (Finnish) population (AF= 0.212418; MAF= 21.24183%, 5330/25092 alleles, homozygotes = 561); grpmax FAF= 0.170731.
This variant is present in gnomAD-Canada v1.0 (AF= 0.1482608695652174, 2728/18400 alleles, homozygotes = 222).
The variant is a missense SNV, p.(Val174Ala), so the generic missense path applies and REVEL is the sole permitted predictor path for PP3/BP4. REVEL is 0.221, which is at or below the generic BP4 supporting threshold of <= 0.29; the SpliceAI result and BayesDel score are not used for this missense criterion. BP4 is met at supporting strength.
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc)
The variant is a missense SNV, p.(Val174Ala), so the generic missense path applies and REVEL is the sole permitted predictor path for PP3/BP4. REVEL is 0.221, below the generic PP3 supporting threshold of >= 0.644; the SpliceAI result and BayesDel score are not used for this missense criterion. The criterion is therefore not met.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.).
BP7 (Richards et al. 2015, PMID:25741868) is defined for a synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence and the nucleotide is not highly conserved. NM_006446.5:c.521T>C in SLCO1B1 is a missense substitution predicted to produce NP_006437.3:p.(Val174Ala). As a result, the encoded protein sequence is altered, so the criterion's silent-variant premise does not hold regardless of any splicing prediction, so BP7's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP7 for SLCO1B1, so the generic ACMG/AMP 2015 definition applies. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.
deterministic_prefilter: requires_synonymous
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.10). REVEL score = 0.221. BayesDel score = -0.413812.
8 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
When these seven SNPs were tested in dominant models, one SNP in SLCO1B1 (SLCO1B1*5, rs4149056, V174A) was associated with the the CAE during the STRENGTH trial (χ2 = 4.2, p = 0.03, FDR = 0.24).
Results, paragraph describing associations between candidate SNPs and the composite adverse event
The valine to alanine substitution at amino acid 174 that is introduced by this SNP appears to be a functionally important variant, as individuals heterozygous or homozygous for this SNP have increased concentrations of drug in plasma after oral administration of a variety of statins.
Introduction; Results; Discussion
Binary logistic regression (Table 2) demonstrated a significant risk per SLCO1B1 c.521 C allele for all myopathy cases regardless of prescribed statin (n = 76; odds ratio (OR) = 2.08 (1.35–3.23), P = 0.005).
Results, SNP analysis; Discussion
the *5 allele (p.Val174Ala, 521T > C, rs4149056) has been shown to interfere with localization of the transporter to the plasma membrane
Introduction; Table 2; Table 3; Discussion
The C allele was present in 21% of FH patients with muscle symptoms versus 16% with no muscle symptoms and the C allele was not associated with the risk of statin-associated muscle symptoms (OR 1.40, [95% CI 0.74–2.64], p = 0.3) in this FH patient sample.
Results, section “SLCO1B1 rs4149056 Genotyping”
only the SNP in SLCO1B1 [rs4149056, (c.521T>C; V174A)] was associated with SRM (P=0.010).
Results, Environment-gene association with SRM, page 6
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
This variant is present in gnomAD v4.1 (AF= 0.14229; MAF= 14.22903%, 228311/1604544 alleles, homozygotes = 17896) and has highest observed frequency in the European (Finnish) population (AF= 0.208479; MAF= 20.84792%, 13336/63968 alleles, homozygotes = 1355); grpmax FAF= 0.195837.
This variant is present in gnomAD v2.1 (AF= 0.133191; MAF= 13.31914%, 37601/282308 alleles, homozygotes = 2959) and has highest observed frequency in the European (Finnish) population (AF= 0.212418; MAF= 21.24183%, 5330/25092 alleles, homozygotes = 561); grpmax FAF= 0.170731.
This variant is present in gnomAD-Canada v1.0 (AF= 0.1482608695652174, 2728/18400 alleles, homozygotes = 222).
This variant has been reported in ClinVar as Benign (7 clinical laboratories) and as Likely benign (1 clinical laboratory) and as other (1 clinical laboratory) and as drug response by ClinPGx (expert panel). (ClinVarID = 37346)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.10). REVEL score = 0.221. BayesDel score = -0.413812.
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV57010105, n = 18 times).
This variant does not lie in a statistically significant hotspot.