The CFTR NM_000492.4:c.1624G>T (NP_000483.3:p.(Gly542Ter)) nonsense variant has not previously been reported in somatic cancers (COSMIC). This variant is predicted to result in an absent or disrupted protein product. Based on available guidelines, this variant is considered to be Pathogenic. This variant is considered to be Pathogenic by the VCEP (CFTR2; ClinVar ID 7115).
Five-step scale from benign to pathogenic. This variant is pathogenic. Select a step to read what it means.
Pathogenic.A pathogenic 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.CFTR encodes an ATP-binding cassette family protein that functions as a chloride channel, helping regulate salt and water movement across epithelial tissues. Disruption of CFTR causes cystic fibrosis, an inherited disorder affecting the lungs, digestive system, and other organs; CFTR has no established 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.
Met, very strong: CFTR c.1624G>T is an exon 12 nonsense variant causing p.Gly542Ter in a gene with an established germline loss-of-function disease mechanism.
Met: G542X occurred in 14/370 French CF chromosomes versus 476/1,178,404 gnomAD NFE alleles, OR 93.67 (95% CI 54.52–160.93), exceeding OR >5 with CI excluding 1.
Met: the exact CFTR c.1624G>T variant has a Pathogenic CFTR2 expert-panel classification in ClinVar, satisfying the supplied PP5 rule.
No benign criterion marked as applied in the recorded assessment.
Pathogenic: PVS1 very strong plus PS4 strong satisfy the generic ACMG/AMP rule for Pathogenic; PP5 supporting provides additional pathogenic evidence.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 585 / 1,612,120 alleles. Recorded AF 0.000362876. Recorded homozygote count 0.
This variant is present in gnomAD v2.1 (AF= 0.000322338; MAF= 0.03223%, 91/282312 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.0014476; MAF= 0.14476%, 15/10362 alleles, homozygotes = 0); grpmax FAF= 0.00055223.
Not available in gnomAD-Canada v1.0.
Recorded SpliceAI maximum delta score: 0.130. Refer to the recorded PP3/BP4 rationale for interpretation.
33 Pathogenic · 2 pathogenic. ClinVar API review status: practice guideline.
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: 3 met · 6 not met · 9 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Neither PS3 nor BS3 is assessed because the reviewed studies do not report a validated, variant-specific functional result for CFTR c.1624G>T/p.G542*.
Clinical observations and general nonsense-variant mechanism evidence were not used as substitutes for the required functional-study evidence.
PS4 is met at strong strength because the verified affected-case frequency for G542X compared with gnomAD NFE gives OR 93.67 (95% CI 54.52-160.93), exceeding the ACMG OR >5.0 threshold with the CI excluding 1.
PP5 is met at supporting strength from the exact-variant CFTR2 expert-panel Pathogenic classification in ClinVar.
PP4 and BP5 are not assessed because the required patient-specific phenotype/family-history and alternate-molecular-basis evidence are unavailable; BP6 is not met because the exact-variant expert-panel classification is Pathogenic rather than benign.
Population evidence does not meet BA1, BS1, BS2, or PM2: the variant is rare but present above the PM2 cutoff, below benign-frequency thresholds, and has no observed homozygotes.
No criteria match.
PVS1 is met at full strength. NM_000492.4:c.1624G>T is a nonsense variant in the relevant CFTR transcript, producing NP_000483.3:p.(Gly542Ter) / p.(G542*), a premature termination well before the normal protein terminus. The affected exon is exon 12, not a distal terminal exon, and the available evidence supports CFTR loss of function as a germline disease mechanism. This is therefore a qualifying null variant with no case-specific evidence of NMD escape, rescue by an alternatively spliced transcript, repeat-region ambiguity, or a biologically non-critical exon that would trigger a downgrade. No named downgrade rule applies.
PVS1: Null variant (nonsense, frameshift, canonical +/−1 or 2 splice sites, initiation codon, single or multi-exon deletion) in a gene where loss of function (LOF) is a known mechanism of disease.
The exact-variant paper PMID:1723032 reports G542X (CFTR c.1624G>T) on 14 of 370 CF chromosomes from 185 unrelated French families. This is a case-control comparison when compared with the matched broad European non-Finnish gnomAD v4.1 population frequency of 476/1,178,404 alleles: using allele-count odds, OR = (14/356)/(476/1,177,928) = 93.67, with an approximate 95% Wald CI of 54.52-160.93. The CI excludes 1 and OR exceeds the ACMG threshold >5.0, so PS4 is met. Human review is requested because gnomAD NFE is a population proxy rather than a study-specific French control cohort and the paper's case denominator is CF chromosomes rather than independently sampled affected individuals.
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.
Expert panel CFTR2 classified as Pathogenic.
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
PM2 is not met under the supplied generic supporting threshold. The generic cutoff is <=0.0001. This variant is present in the default all-comers population sources at AF 0.000322338 in gnomAD v2.1 and 0.000362876 in gnomAD v4.1, both above the cutoff. No governing VCEP specifies a non-cancer or exome-only source for this generic interpretation.
Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
BA1 is not met. The generic stand-alone benign threshold is >=0.05. The applicable gnomAD all-comers filtering frequencies are grpmax FAF 0.00055223 in v2.1 and 0.00048844 in v4.1; both are far below 0.05. The highest observed Ashkenazi Jewish point estimates, 0.0014476 from 15/10362 alleles in v2.1 and 0.00135272 from 40/29570 alleles in v4.1, are not used because the required measure is grpmax FAF, and both source populations exceed 2000 observed alleles. The variant also has a pathogenic ClinVar practice-guideline consensus, so the low frequency does not justify a stand-alone benign conclusion.
Allele frequency is above 5% in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
BS1 is not met. The generic default threshold is grpmax FAF >=0.01, while the applicable gnomAD all-comers grpmax FAF values are 0.00055223 in v2.1 and 0.00048844 in v4.1. The relevant populations contributing the maximum FAF have more than 2000 observed alleles. The Ashkenazi Jewish point estimates are not substituted for grpmax FAF. CFTR-related cystic fibrosis is an early-onset autosomal-recessive disorder with substantial allelic heterogeneity, but no maximum-credible-frequency calculation is needed to reject BS1 because the filtering frequencies are already well below the supplied 1% default.
Allele frequency is greater than expected for the disorder.
BS2 is not met. For this recessive disorder, the qualifying observation would be a healthy adult homozygote. gnomAD reports zero homozygotes in v2.1 (91/282312 alleles) and v4.1 (585/1612120 alleles), and no healthy adult homozygous observation is provided elsewhere in the supplied evidence.
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.
BP2 requires either observation in trans with a pathogenic variant in a fully penetrant dominant gene/disorder or observation in cis with a pathogenic variant in any inheritance pattern. CFTR-related cystic fibrosis is a recessive disorder, and PMID:1723032 reports G542X in compound-heterozygous configurations, which is trans evidence in a recessive context rather than the dominant-trans BP2 configuration. No cis observation with a pathogenic variant is reported in the available evidence. BP2 is therefore not met.
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 exact-variant ClinVar record has a Pathogenic CFTR2 expert-panel classification, not a Benign or Likely benign expert-panel classification. No exact-variant benign expert-panel assertion was identified; ordinary laboratory submissions, aggregate labels, and non-expert assertions were not used to trigger BP6. Therefore 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.
PS2 cannot be assessed because the available evidence does not document a disease-affected proband with confirmed maternity and paternity, a de novo occurrence, or absence of family history. The available variant-specific literature reports G542X in affected CF chromosomes but does not provide the required parentage and de novo testing for this case.
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
PS3 cannot be assessed from the available evidence. PMID:23974870 describes premature-termination-codon consequences and functional classification of CFTR variants generally, but does not explicitly study c.1624G>T/p.G542*. PMID:7691345 experimentally evaluates other CFTR variants (ΔF508 and G551D), not G542X. No validated, reproducible in vitro or in vivo assay with variant-specific controls and a result for G542X was identified, so the evidence does not establish the PS3 requirement.
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
PM3 is applicable to the recessive CFTR disorder when the variant is demonstrated in trans with a pathogenic variant. PMID:1723032 reports seven patients described as compound heterozygotes for ΔF508/G542X and seven as G542X/x, which supports an allelic trans configuration for G542X in affected individuals. However, the available extraction does not document testing of parents or offspring establishing phase, and it does not identify the partner variants in the G542X/x group or independently establish the pathogenicity of each partner variant. The required phase evidence is therefore insufficient for a definitive PM3 assessment.
For recessive disorders, detected in trans with a pathogenic variant ... This requires testing of parents (or offspring) to determine phase.
PM6 cannot be assessed because the available evidence does not establish an assumed de novo variant in a patient with the disease. No case-specific parental testing or documentation of de novo status is provided; the literature only reports the variant in affected CF chromosomes without establishing de novo origin.
Assumed de novo, but without confirmation of paternity and maternity.
PP1 cannot be assessed because no multiple affected family members with variant-status data are documented. PMID:1723032 reports G542X in 14 CF chromosomes from 185 unrelated French families, including seven patients with deltaF508/G542X and seven with G542X/x, but this is a population screening study and does not provide case-specific co-segregation across affected relatives or meioses.
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease. ... Note: May be used as stronger evidence with increasing segregation data.
The generic PP4 rule requires a patient's phenotype or family history that is highly specific for a disease with a single genetic etiology. The available case evidence identifies the variant and CFTR-related disease context but does not provide a patient-specific phenotype or family history sufficiently detailed to evaluate this criterion.
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
BS3 cannot be assessed from the available evidence. The reviewed functional literature did not provide a well-established assay showing that CFTR c.1624G>T/p.G542* has no damaging effect on protein function or splicing. PMID:23974870 discusses premature-termination-codon consequences generally, while PMID:7691345 tests different CFTR variants; neither supplies a benign, variant-specific functional result for G542X.
Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
BS4 cannot be assessed because no affected family members lacking the variant are documented. The available G542X literature does not provide a family pedigree, affected relatives tested for the variant, or a non-segregation observation that could establish lack of segregation.
Lack of segregation in affected members of a family.
No evidence in the reviewed case materials demonstrates that this exact variant was found in a case with an alternate molecular basis for disease. The CFTR expert-panel classification and disease-associated reports are not evidence of an alternate molecular basis, so BP5 cannot be assessed.
Variant found in a case with an alternate molecular basis for disease.
PS1 (Richards et al. 2015, PMID:25741868) requires the same amino acid change as a previously established pathogenic variant, evaluated regardless of the underlying nucleotide change. NM_000492.4:c.1624G>T in CFTR is a nonsense substitution introducing a premature stop codon predicted to produce NP_000483.3:p.(Gly542Ter). As a result, no altered amino acid exists at this position to compare against any previously established pathogenic missense variant, so PS1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PS1 for CFTR, 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_missense
PM1 (Richards et al. 2015, PMID:25741868) applies to a missense variant located in a mutational hot spot and/or a critical, well-established functional domain without benign variation. NM_000492.4:c.1624G>T in CFTR is a nonsense substitution introducing a premature stop codon predicted to produce NP_000483.3:p.(Gly542Ter). As a result, no altered residue exists to evaluate for mutational hot-spot or critical-domain membership, so PM1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM1 for CFTR, 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_missense
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_000492.4:c.1624G>T in CFTR is a nonsense substitution introducing a premature stop codon predicted to produce NP_000483.3:p.(Gly542Ter). 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 CFTR, 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
PM5 (Richards et al. 2015, PMID:25741868) requires a novel missense change at an amino acid residue where a different missense change has previously been determined to be pathogenic. NM_000492.4:c.1624G>T in CFTR is a nonsense substitution introducing a premature stop codon predicted to produce NP_000483.3:p.(Gly542Ter). As a result, no missense change exists at this residue to compare against a different pathogenic missense change at the same position, so PM5's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PM5 for CFTR, 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_missense
PP2 (Richards et al. 2015, PMID:25741868) applies to a missense variant in a gene with a low rate of benign missense variation, where missense variants are a common mechanism of disease. NM_000492.4:c.1624G>T in CFTR is a nonsense substitution introducing a premature stop codon predicted to produce NP_000483.3:p.(Gly542Ter). As a result, the gene's missense-constraint properties are irrelevant because no missense change is present to evaluate, so PP2's structural prerequisite is not met by this variant class. No VCEP criteria specification covers PP2 for CFTR, 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_missense
PP3 is not applicable because NM_000492.4:c.1624G>T is a nonsense variant, producing NP_000483.3:p.(G542*), and the governing generic scope excludes nonsense and other truncating/protein-length-changing variants. The available SpliceAI max delta of 0.13 is therefore not used for PP3; no REVEL path applies.
PP3/BP4 apply only to a missense variant, or to a splice-region/intronic variant via the SpliceAI path - never to a frameshift, nonsense, or other truncating/protein-length-changing variant.
BP1 (Richards et al. 2015, PMID:25741868) applies to a missense variant in a gene for which primarily truncating variants are known to cause disease. NM_000492.4:c.1624G>T in CFTR is a nonsense substitution introducing a premature stop codon predicted to produce NP_000483.3:p.(Gly542Ter). As a result, the gene's truncating-variant mechanism is irrelevant because no missense change is present to evaluate, so BP1's structural prerequisite is not met by this variant class. No VCEP criteria specification covers BP1 for CFTR, 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_missense
BP3 (Richards et al. 2015, PMID:25741868) applies to in-frame insertions/deletions located in a repetitive region without a known function. NM_000492.4:c.1624G>T in CFTR is a nonsense substitution introducing a premature stop codon predicted to produce NP_000483.3:p.(Gly542Ter). 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 CFTR, 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
BP4 is not applicable because NM_000492.4:c.1624G>T is a nonsense variant, producing NP_000483.3:p.(G542*), and BP4 does not cover truncating variants. The SpliceAI max delta of 0.13 cannot provide BP4 because absence of a strong predicted splice effect does not negate the truncating protein consequence; splice prediction for this variant is relevant only to PVS1-type rescue assessment.
BP4 on a frameshift or nonsense variant is not_applicable: a 'no predicted splice impact' result leaves the truncating protein effect in place, so it is not evidence of no impact on the gene product - a splice prediction for such a variant matters only to PVS1 (e.g. predicted rescue).
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_000492.4:c.1624G>T in CFTR is a nonsense substitution introducing a premature stop codon predicted to produce NP_000483.3:p.(Gly542Ter). 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 CFTR, 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 CFTR, mapped onto the exon structure of NM_000492.4. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| Ashkenazi Jewish40 / 29,570 | 0.0014 |
| Admixed American39 / 59,920 | 0.00065 |
| European (non-Finnish)476 / 1,178,404 | 0.0004 |
| Remaining individuals25 / 62,416 | 0.0004 |
| Middle Eastern1 / 6,046 | 0.00017 |
| African/African American3 / 74,990 | 4e-05 |
| South Asian1 / 91,052 | 1.1e-05 |
| Ashkenazi Jewish15 / 10,362 | 0.0014 |
| Admixed American27 / 35,300 | 0.00076 |
| European (non-Finnish)46 / 128,830 | 0.00036 |
| Remaining individuals2 / 7,200 | 0.00028 |
| African/African American1 / 24,966 | 4e-05 |
This variant is present in gnomAD v4.1 (AF= 0.000362876; MAF= 0.03629%, 585/1612120 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00135272; MAF= 0.13527%, 40/29570 alleles, homozygotes = 0); grpmax FAF= 0.00048844.
This variant is present in gnomAD v2.1 (AF= 0.000322338; MAF= 0.03223%, 91/282312 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.0014476; MAF= 0.14476%, 15/10362 alleles, homozygotes = 0); grpmax FAF= 0.00055223.
Not available in gnomAD-Canada v1.0.
PP3 is not applicable because NM_000492.4:c.1624G>T is a nonsense variant, producing NP_000483.3:p.(G542*), and the governing generic scope excludes nonsense and other truncating/protein-length-changing variants. The available SpliceAI max delta of 0.13 is therefore not used for PP3; no REVEL path applies.
PP3/BP4 apply only to a missense variant, or to a splice-region/intronic variant via the SpliceAI path - never to a frameshift, nonsense, or other truncating/protein-length-changing variant.
BP4 is not applicable because NM_000492.4:c.1624G>T is a nonsense variant, producing NP_000483.3:p.(G542*), and BP4 does not cover truncating variants. The SpliceAI max delta of 0.13 cannot provide BP4 because absence of a strong predicted splice effect does not negate the truncating protein consequence; splice prediction for this variant is relevant only to PVS1-type rescue assessment.
BP4 on a frameshift or nonsense variant is not_applicable: a 'no predicted splice impact' result leaves the truncating protein effect in place, so it is not evidence of no impact on the gene product - a splice prediction for such a variant matters only to PVS1 (e.g. predicted rescue).
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_000492.4:c.1624G>T in CFTR is a nonsense substitution introducing a premature stop codon predicted to produce NP_000483.3:p.(Gly542Ter). 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 CFTR, 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 = 0.13). BayesDel score = 0.66.
10 paper records listed. 4 cited in the classification.
G542X was found in 14 patients, with 7 compound heterozygotes dF508/G542X, and 7 compound heterozygotes G542X/x. In all cases it was associated with haplotype B.
Location Results, Population Screening; Table 1; Prenatal Diagnosis
Context Allele-specific oligonucleotide hybridization screening of 13 CFTR mutations in 370 CF chromosomes from 185 unrelated French families; RFLP haplotyping at linked XV-2c and KM19 markers; one prenatal-diagnosis application using G542X-specific probes.
A common consequence of a PTC variant is nonsense-mediated decay (NMD) of mRNA, resulting in a severe reduction in mRNA levels and no protein produced.
Location Results, Functional analysis, paragraph beginning “A common consequence of a PTC variant”
Context CFTR2 phenotype-driven study of 39,696 individuals with cystic fibrosis; functional classification included predicted premature-termination-codon effects, clinical sweat-chloride analysis, and other CFTR functional assays.
A novel heterozygous nonsense variant in the CFTR gene would likely be considered a recessive pathogenic variant.
Location Proposed Criteria for Interpretation of Sequence Variants, PVS1 Null variants
DNA was tested for 16 CFTR mutations — ΔF508, W1282X, R117H, 621+1(G→T), R334W, R347P, A455E, ΔI507, 1717−1(G→A), G542X, S549N, G551D, R553X, R560T, N1303K, and 3849+10Kb(C→T) — using reverse dot blot strips.
Location Methods, DNA Studies; Results, paragraph 1
Context Blood-DNA testing in 27 patients referred for idiopathic chronic pancreatitis evaluation; 17 CFTR mutations were assayed by reverse dot blot, with detected alleles ΔF508, R117H, and N1303K.
This report provides a thorough characterization of two mutant CFTR proteins, AF508 and G551D, in stably transduced cells studied by biochemical, cell biological, and physiological methods.
Discussion, first paragraph; Results sections on intracellular processing, subcellular localization, and functional analyses
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= 0.000362876; MAF= 0.03629%, 585/1612120 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00135272; MAF= 0.13527%, 40/29570 alleles, homozygotes = 0); grpmax FAF= 0.00048844.
This variant is present in gnomAD v2.1 (AF= 0.000322338; MAF= 0.03223%, 91/282312 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.0014476; MAF= 0.14476%, 15/10362 alleles, homozygotes = 0); grpmax FAF= 0.00055223.
Not available in gnomAD-Canada v1.0.
This variant has been reported in ClinVar as Pathogenic (33 clinical laboratories) and as pathogenic (2 clinical laboratories) and as Pathogenic by CFTR2 (expert panel). (ClinVarID = 7115)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.13). BayesDel score = 0.66.
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.