The HBB NM_000518.5:c.79G>A (NP_000509.1:p.(Glu27Lys)) missense variant has not previously been reported in somatic cancers (COSMIC). Based on available guidelines, this variant is considered to be a Variant of Uncertain Significance (VUS).
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.HBB encodes the beta-globin protein, one of the two types of chains that combine with alpha-globin to form adult hemoglobin, which carries oxygen in the blood. Abnormal or absent beta-globin is associated with sickle cell disease and beta-thalassemia. HBB has no established cancer role.
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.
Met: affected-versus-matched-ancestry control counts yield OR 188.51 (95% CI 139.95-253.93), and 188.51 > 5.0 with the interval excluding 1.0.
Met at supporting strength: REVEL 0.721 meets the missense PP3 threshold of >=0.644.
No benign criterion marked as applied in the recorded assessment.
VUS: PS4 (strong) plus PP3 (supporting) do not satisfy any generic ACMG/AMP pathogenic, likely pathogenic, or benign combination rule.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 361 / 1,613,724 alleles. Recorded AF 0.000223706. Recorded homozygote count 5.
This variant is present in gnomAD v2.1 (AF= 0.000233415; MAF= 0.02334%, 66/282758 alleles, homozygotes = 1) and has highest observed frequency in the East Asian population (AF= 0.00120397; MAF= 0.12040%, 24/19934 alleles, homozygotes = 0); grpmax FAF= 0.00089997.
This variant is present in gnomAD-Canada v1.0 (AF= 0.0010315995222065371, 19/18418 alleles, homozygotes = 1).
Recorded REVEL score: 0.721. Refer to the recorded PP3/BP4 rationale for interpretation.
36 Pathogenic. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
No standalone functional evidence summary is recorded in evidence_summary.functional.
This variant has not previously been reported in somatic cancers (COSMIC).
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: 2 met · 8 not met · 14 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
This group evaluates only PS1, PM1, PM5, PP2, and BP1 under generic ACMG/AMP because the listed HBB VCEP specification has no released criteria.
No additional criterion is adjudicated.
Generic ACMG/AMP rules govern because the listed HBB ClinGen Hemoglobinopathy Expert Panel specification has no released criterion rules.
PS4 is met from a computed affected-versus-matched-ancestry control comparison using PMID:27828729 and gnomAD v4.1 counts.
PP5 and BP6 are not triggered because the exact-variant ClinVar audit has no expert-panel assertion; laboratory submissions and aggregate labels are excluded.
PP4 and BP5 remain not assessed because the required patient phenotype/family-history and alternate-molecular-basis evidence is not provided.
The variant is missense, so PP3 and BP4 use REVEL only; REVEL 0.721 supports PP3 at supporting strength but does not meet BP4.
No criteria match.
The governing ACMG/AMP rule is: "The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls. Note 1: 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." PMID:27828729 reports HBB:c.79G>A (CD26(G>A)) in 79 of 241 mutant alleles among 120 Bengali patients with thalassemia major or intermedia. Using the matched-ancestry South Asian gnomAD v4.1 allele count of 235/91,080 as the control frequency, the allele-count odds ratio is (79/162)/(235/90,845) = 188.51, with an approximate 95% CI of 139.95-253.93. The comparison is explicit: OR 188.51 > 5.0, and the 95% CI 139.95-253.93 does not include 1.0; therefore PS4 is met. This is a case-control comparison computed from affected-cohort and matched-ancestry population counts, even though the paper does not print an OR. The other literature-pass papers indexed for PS4 were verified and did not provide a stronger exact-variant case-control estimate.
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.
NM_000518.5:c.79G>A is a missense variant, NP_000509.1:p.(Glu27Lys), so the governing generic rule requires the missense REVEL path only. REVEL is 0.721, which meets the supplied ClinGen SVI supporting PP3 threshold of >= 0.644 from Pejaver et al. 2022 (PMID:36413997). The SpliceAI max delta of 0.758 is not used for PP3 because splice prediction is not the applicable path for a missense variant; BayesDel is not available for generic ACMG strength calibration.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.).
Generic PM2 is not met because the variant is present in multiple population datasets at frequencies above the generic supporting threshold of <=0.0001. gnomAD v4.1 reports AF 0.000223706 overall, gnomAD v2.1 reports AF 0.000233415 overall, and gnomAD v2.1 non-cancer exomes report AF 0.000257586; the variant is therefore neither absent nor at or below 0.0001 in the applicable default population data. The gnomAD v4.1 South Asian AF is 0.002580149, with four homozygotes.
PM2 (supporting): <= 0.0001 — SVI recommendation to downgrade PM2 to Supporting (ClinGen SVI 2020) (PMID:25741868)
The observed missense variant affects residue 27, but no different missense substitution at that residue was determined to be pathogenic in the reviewed evidence. PMID:15481887 discusses Hb Tripoli (Glu>Ala) at the same legacy codon and explicitly states that only Hb E was clearly associated with a thalassemic phenotype; this does not provide a pathogenic alternate-residue comparator. The PM5 candidate collection also contains zero same-residue candidates.
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.
The governing ACMG/AMP rule is: "Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation." Exact-variant ClinVar records show Pathogenic submissions from clinical laboratories, but the audit reports zero expert-panel submissions and no exact-variant expert-panel classification. PMID:25052315 is a best-practice guideline and does not report this exact variant. Ordinary laboratory submissions, aggregate labels, and non-expert assertions do not satisfy the required PP5 trigger.
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
Generic BA1 is not met. The variant is present in gnomAD v2.1 at AF 0.000233415 overall and highest population AF 0.001203973 in East Asians, and in gnomAD v4.1 at AF 0.000223706 overall and highest population AF 0.002580149 in South Asians; the highest observed frequency is far below the generic stand-alone threshold of >=0.05. The gnomAD v2.1 non-cancer exome frequency is also only 0.000257586, below 0.05.
BA1 (stand-alone): >= 0.05 — ACMG/AMP 2015 stand-alone benign allele frequency (PMID:25741868)
Generic BS1 is not met on the available population data. The variant frequency is 0.000223706 overall in gnomAD v4.1, 0.002580149 in the highest population (South Asian), and 0.000257586 in gnomAD v2.1 non-cancer exomes, all below the generic 0.01 default. The South Asian enrichment is consistent with the known HbE allele distribution and the recessive HBB disease context; no prevalence, penetrance, allelic-heterogeneity, or maximum-credible-allele-frequency inputs were supplied that would justify a different disorder-specific threshold. A Bengali thalassemia patient cohort reported HBB:c.79G>A among 79 of 241 mutant alleles (32.78%), which documents ancestry-associated disease allele enrichment but is not a population-control frequency and cannot by itself establish BS1.
Allele frequency is greater than expected for the disorder.
The available HBB evidence does not support a gene for which primarily truncating variants are known to cause disease. Instead, the reviewed material documents disease-associated point/missense variation, including HBB Glu27Lys (Hb E), and describes numerous structural hemoglobin variants. Therefore this missense variant is not in the gene-level situation specified by BP1.
Missense variant in a gene for which primarily truncating variants are known to cause disease.
NM_000518.5:c.79G>A is a missense variant, so BP4 must be assessed through the missense REVEL path only. REVEL is 0.721, above the supplied generic BP4 supporting cutoff of <= 0.29 from Pejaver et al. 2022 (PMID:36413997), and therefore does not support BP4. The SpliceAI max delta of 0.758 is not substituted because splice prediction is not the applicable path for a missense variant; BayesDel is not available for generic ACMG strength calibration.
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc)
The governing ACMG/AMP rule is: "Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation." The exact-variant ClinVar record contains no expert-panel benign or likely-benign classification; instead, its audited laboratory submissions are Pathogenic. No reputable exact-variant benign report was identified, so BP6 is not met.
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
The variant is NP_000509.1:p.(Glu27Lys), but the available evidence does not identify a different nucleotide change producing the same amino-acid substitution that has been independently established as pathogenic. The ClinVar-linked literature identifies the observed HBB:c.79G>A allele itself, not a distinct nucleotide-level PS1 comparator. A targeted same-amino-acid comparator record is therefore still needed; the identical variant cannot serve as its own PS1 comparator.
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.
The available case evidence does not document an affected proband with this variant established as de novo, nor does it provide confirmed maternity and paternity. Without both parental relationships confirmed and the variant absent in both biological parents, the generic PS2 definition cannot be assessed.
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
The available literature describes a mechanistic splice consequence for the Hb E allele (legacy HBB Glu26Lys, corresponding to NM_000518.5:c.79G>A / p.Glu27Lys), including creation of a cryptic donor splice site, aberrant beta-globin transcript splicing, and reduced betaE-mRNA production. However, the reviewed source is a clinical review that attributes these findings to prior studies and does not itself provide a validated, reproducible variant-specific functional assay with assay controls, quantitative results, or diagnostic-laboratory validation. Therefore, the evidence does not establish PS3 under the required well-established functional-study definition, and the criterion is not assessed rather than met or not met.
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
The HBB VCEP specification is listed but has no released criteria, and vcep_materials.json contains no HBB domain-table entry. The generic rule requires a mutational hotspot or a critical, well-established functional domain without benign variation. The case evidence reports no statistically significant hotspot for residue E27, and it does not establish a qualifying critical-domain/no-benign-variation finding for residue 27. The criterion therefore cannot be concluded from the available evidence.
Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.
The variant is reported in affected thalassemia patients in compound-heterozygous genotypes with HBB:c.92+5G>C and other beta-thalassemia alleles. In PMID:27828729, CD26(G>A) [HBB:c.79G>A] and IVS1-5(G>C) [HBB:c.92+5G>C] are listed as a compound-heterozygous genotype in 60 patients, and additional compound-heterozygous HbE/beta-thalassemia genotypes are listed. However, the available report does not document parental or offspring testing to establish phase, which the governing PM3 note expressly requires; therefore the observations cannot be used to assign PM3 without confirmed trans phase.
For recessive disorders, detected in trans with a pathogenic variant ... This requires testing of parents (or offspring) to determine phase.
The available case evidence does not document an assumed de novo occurrence in an affected proband. There are no reported parental genotypes or other case-level findings showing that the variant arose de novo without confirmation of maternity and paternity, so PM6 cannot be assessed.
Assumed de novo, but without confirmation of paternity and maternity.
The available evidence does not report affected family members, their genotypes, or transmission of NM_000518.5:c.79G>A through a family. Because no co-segregation observations or meioses are available, PP1 cannot be assessed under the generic definition.
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease.
HBB missense/structural variants are documented in the reviewed material, including the disease-associated Hb E missense allele, but the evidence does not establish both required PP2 components: a low rate of benign missense variation for HBB and missense variants as a common disease mechanism under a gene-level comparison. The observed variant's population frequency cannot substitute for a gene-level benign-missense-rate assessment.
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 governing ACMG/AMP rule is: "Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology." The available case evidence identifies the HBB variant but does not provide the patient's phenotype, family history, or a sufficiently specific disease presentation for assessment under PP4.
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
BS2 cannot be assessed from the available data. gnomAD reports one homozygote in v2.1, one homozygote in the v2.1 non-cancer exomes, and five homozygotes in v4.1, including four South Asian homozygotes, but these database records do not document that the individuals were healthy adults, their ages, clinical status, or absence of HBB-related disease. Therefore the observations do not establish the required healthy-adult homozygous state for a recessive disorder.
Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
No reviewed source provides a well-established functional study showing that HBB c.79G>A has no damaging effect on protein function or splicing. The available Hb E review instead describes a cryptic splice site, aberrant beta-globin transcript splicing, and reduced betaE-mRNA production, but it does not provide the controlled assay design and quantitative evidence required to evaluate BS3. Consequently, BS3 is not assessed.
Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
The available evidence does not identify affected family members who were tested for NM_000518.5:c.79G>A and found not to carry it. Therefore, no lack-of-segregation observation is available for BS4; phenocopy and the possibility of more than one pathogenic variant also cannot be evaluated.
Lack of segregation in affected members of a family.
The available evidence reports HBB:c.79G>A in compound-heterozygous, recessive thalassemia genotypes, not in cis with another pathogenic variant. No evidence establishes a fully penetrant dominant HBB disorder for which the variant was observed in trans with a pathogenic variant, and no parental or molecular phasing data establish cis. The BP2 applicability requirements are therefore not demonstrated.
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 governing ACMG/AMP rule is: "Variant found in a case with an alternate molecular basis for disease." The available evidence does not document an individual case carrying HBB:c.79G>A in which an alternate molecular basis for that disease was established; population frequency and thalassemia-cohort data do not establish BP5.
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_000518.5:c.79G>A in HBB is a missense substitution predicted to produce NP_000509.1:p.(Glu27Lys). 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 HBB, 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_000518.5:c.79G>A in HBB is a missense substitution predicted to produce NP_000509.1:p.(Glu27Lys). 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 HBB, 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_000518.5:c.79G>A in HBB is a missense substitution predicted to produce NP_000509.1:p.(Glu27Lys). 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 HBB, 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_000518.5:c.79G>A in HBB is a missense substitution predicted to produce NP_000509.1:p.(Glu27Lys). 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 HBB, 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 HBB, mapped onto the exon structure of NM_000518.5. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| South Asian235 / 91,080 | 0.00264 hom |
| Remaining individuals70 / 62,492 | 0.00111 hom |
| East Asian38 / 44,870 | 0.00085 |
| Middle Eastern3 / 6,058 | 0.0005 |
| African/African American5 / 75,032 | 6.7e-05 |
| Admixed American2 / 60,024 | 3.3e-05 |
| European (non-Finnish)8 / 1,179,604 | 6.8e-06 |
| East Asian24 / 19,934 | 0.0012 |
| South Asian35 / 30,616 | 0.00111 hom |
| Remaining individuals2 / 7,222 | 0.00028 |
| African/African American2 / 24,968 | 8e-05 |
| Admixed American2 / 35,436 | 5.6e-05 |
| European (non-Finnish)1 / 129,092 | 7.7e-06 |
This variant is present in gnomAD v4.1 (AF= 0.000223706; MAF= 0.02237%, 361/1613724 alleles, homozygotes = 5) and has highest observed frequency in the South Asian population (AF= 0.00258015; MAF= 0.25801%, 235/91080 alleles, homozygotes = 4); grpmax FAF= 0.00230876.
This variant is present in gnomAD v2.1 (AF= 0.000233415; MAF= 0.02334%, 66/282758 alleles, homozygotes = 1) and has highest observed frequency in the East Asian population (AF= 0.00120397; MAF= 0.12040%, 24/19934 alleles, homozygotes = 0); grpmax FAF= 0.00089997.
This variant is present in gnomAD-Canada v1.0 (AF= 0.0010315995222065371, 19/18418 alleles, homozygotes = 1).
NM_000518.5:c.79G>A is a missense variant, NP_000509.1:p.(Glu27Lys), so the governing generic rule requires the missense REVEL path only. REVEL is 0.721, which meets the supplied ClinGen SVI supporting PP3 threshold of >= 0.644 from Pejaver et al. 2022 (PMID:36413997). The SpliceAI max delta of 0.758 is not used for PP3 because splice prediction is not the applicable path for a missense variant; BayesDel is not available for generic ACMG strength calibration.
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.).
NM_000518.5:c.79G>A is a missense variant, so BP4 must be assessed through the missense REVEL path only. REVEL is 0.721, above the supplied generic BP4 supporting cutoff of <= 0.29 from Pejaver et al. 2022 (PMID:36413997), and therefore does not support BP4. The SpliceAI max delta of 0.758 is not substituted because splice prediction is not the applicable path for a missense variant; BayesDel is not available for generic ACMG strength calibration.
Multiple lines of computational evidence suggest no impact on 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_000518.5:c.79G>A in HBB is a missense substitution predicted to produce NP_000509.1:p.(Glu27Lys). 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 HBB, 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 possible splice impact for this variant (max delta score = 0.76). REVEL score = 0.721. BayesDel score = 0.241022.
10 paper records listed. 5 cited in the classification.
In addition, several Hb variants have been described at the same position (Table 1), and among these, only Hb E is clearly associated with a thalassemic phenotype (8–11).
Location Discussion of Hb Tripoli, p. 208; Table 1, p. 209
Context Comparative discussion of codon 26 beta-globin variants; the paper directly characterized Hb Tripoli (GAG>GCG; Glu>Ala), not Hb E.
The nucleotide substitution creates a cryptic donor splice site, GTG;GTAAGG, and causes aberrant splicing of the b-globin gene transcripts, [3] a decrease of bE-mRNA production, and a bþ-thalassemia phenotype [26,27].
Location Laboratory Diagnosis, p. 644
Context Clinical review of Hb SE disease and Hb E-related disease; includes clinical HPLC and ARMS diagnosis but summarizes the splice mechanism from cited prior studies rather than reporting a primary controlled functional assay for the variant.
In many Asian populations, the commonest form of severe thalassemia results from the coinheritance of HbE and beta thalassemia.
Location Abstract
Context Asian population study concerning severe thalassemia and malaria-related phenotypic modifiers; full text was not available in the case packet.
In the HBB gene locus, more than 280 genetic variations (variants) causing b-thalassaemia have been described, the majority of which are point variants.
Location The genes and disease-causing variants
Context EMQN best-practice guideline based on haematological/biochemical screening and DNA-analysis methodologies, including PCR-based methods, Sanger sequencing, and variant-characterization techniques.
Two alleles—CD26(G>A) [HBB:c.79G>A] and IVS1-5(G>C) [HBB:c.92 + 5G>C] are very predominant in this population for the manifestation of thalassemia.
Location Discussion; Table 2; Table 3
Context Cross-sectional Sanger-sequencing study of 120 Bengali patients with thalassemia major or intermedia; an 800-bp HBB fragment was amplified and sequenced, and mutant-allele frequencies were tabulated for 241 alleles.
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= 0.000223706; MAF= 0.02237%, 361/1613724 alleles, homozygotes = 5) and has highest observed frequency in the South Asian population (AF= 0.00258015; MAF= 0.25801%, 235/91080 alleles, homozygotes = 4); grpmax FAF= 0.00230876.
This variant is present in gnomAD v2.1 (AF= 0.000233415; MAF= 0.02334%, 66/282758 alleles, homozygotes = 1) and has highest observed frequency in the East Asian population (AF= 0.00120397; MAF= 0.12040%, 24/19934 alleles, homozygotes = 0); grpmax FAF= 0.00089997.
This variant is present in gnomAD-Canada v1.0 (AF= 0.0010315995222065371, 19/18418 alleles, homozygotes = 1).
This variant has been reported in ClinVar as Pathogenic (36 clinical laboratories). (ClinVarID = 15161)
SpliceAI predicts possible splice impact for this variant (max delta score = 0.76). REVEL score = 0.721. BayesDel score = 0.241022.
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
This variant does not lie in a statistically significant hotspot.