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POLEc.6330+19G>ABenign
Print report
Variant interpretation report

POLE c.6330+19G>A, p.?

NM_006231.4:c.6330+19G>A NP_006222.2:p.? View identifiers
Classification
Benign

Variant description:

No variant summary was recorded for this case.

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.

In plain language

Gene-level background from the recorded interpretation.

About POLE

No gene-level summary was recorded for this case.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.
01The reasoning

How it was classified

The recorded framework is León-Castillo et al. 2020 custom POLE framework. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 0 Benign evidence criteria: 3
Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 3
BA1Stand alone
BA1 · stand alone

This variant is present at high frequency in gnomAD population databases. In gnomAD v2.1: overall AF=0.4166% (1169/280568 alleles), African/African American subpopulation AF=4.23% (1052/24896 alleles), grpmax FAF=4.01%, with 16 homozygotes observed. In gnomAD v4.1: overall AF=0.2185% (3498/1600686 alleles), African/African American subpopulation AF=4.17% (3108/74566 alleles), grpmax FAF=4.05%, with 54 homozygotes observed. The grpmax filtering allele frequency exceeds the BA1 threshold of >1% in both datasets, and the observation of multiple homozygotes confirms this is a common population polymorphism incompatible with a Mendelian disease-causing role.

BP4Supporting
BP4 · supporting

SpliceAI predicts no splicing impact for this intronic variant (max delta score = 0.00), indicating that the c.6330+19G>A substitution does not create or disrupt a splice site. In the absence of applicable missense prediction tools (REVEL and BayesDel not available for intronic variants), SpliceAI provides the primary computational evidence for this variant class, and its prediction of no splicing effect supports a benign interpretation.

BP6Supporting
BP6 · supporting

ClinVar reports this variant as Benign (6 clinical laboratories: GeneDx, PreventionGenetics, ARUP Laboratories, KCCC/NGS Laboratory, Labcorp/Invitae, and Center for Genomic Medicine Rigshospitalet). Although review status is 'criteria provided, single submitter' and no expert panel review is recorded, the unanimous classification as Benign across multiple independent clinical laboratories provides supporting evidence for a benign interpretation.

Recorded classification: Benign

BA1 (stand-alone benign) is met: the variant has grpmax filtering allele frequency of 4.01% (gnomAD v2.1) and 4.05% (gnomAD v4.1), exceeding the 1% stand-alone benign threshold, with 16+54 homozygotes observed. Under both the León-Castillo custom POLE framework (rule: 'BA1') and generic ACMG/AMP 2015 combination rules, BA1 alone suffices for a Benign classification. BP4 and BP6 (both supporting benign) provide additional concordant evidence but are not required for the call.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1
gnomAD v2.1
Population frequency
3,498 / 1,600,686 alleles

gnomAD v4.1: 3,498 / 1,600,686 alleles. Recorded AF 0.00218531. Recorded homozygote count 54.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.00416655; MAF= 0.41665%, 1169/280568 alleles, homozygotes = 16) and has highest observed frequency in the African/African American population (AF= 0.0422558; MAF= 4.22558%, 1052/24896 alleles, homozygotes = 15); grpmax FAF= 0.0401049.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.0024445893089960887, 45/18408 alleles, homozygotes = 1).

Applied · BA1 →
gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗
SpliceAI score
0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4 → SpliceAI ↗
ClinVar submissions
6 reported laboratory submissions

6 Benign. ClinVar API review status: criteria provided, multiple submitters, no conflicts.

Applied · BP6 → ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded

No standalone functional evidence summary is recorded in evidence_summary.functional.

No listed criterion applied OncoKB ↗
Somatic evidence
No matching record reported

This variant has not previously been reported in somatic cancers (COSMIC).

Context only COSMIC ↗
For specialists

Technical detail

ACMG/AMP criteria under León-Castillo et al. 2020 custom POLE framework, with the data and sources behind each one.

26 criteria with recorded statuses: 3 met · 9 not met · 0 not assessed · 14 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP4BP5BP6BP7
Met Not met Not assessed Not applicable

NM_006231.4:c.6330+19G>A is classified as Benign.

BA1 is met: the variant has a grpmax filtering allele frequency of 4.01% (gnomAD v2.1) and 4.05% (gnomAD v4.1), exceeding the 1% stand-alone benign threshold. The variant is observed in 1169/280568 alleles (16 homozygotes) in gnomAD v2.1 and 3498/1600686 alleles (54 homozygotes) in gnomAD v4.1, with highest frequency in the African/African American population (4.23% v2.1, 4.17% v4.1).

BP4 (supporting benign) is met: SpliceAI predicts no splicing impact (max delta = 0.00).

BP6 (supporting benign) is met: ClinVar reports this variant as Benign from 6 independent clinical laboratories.

All pathogenic criteria were assessed and are either not met, not applicable, or not supported by the available evidence. PVS1 is not applicable (deep intronic, not a null variant). PM1 is not applicable (not an exonuclease-domain missense hotspot). PM2 is not met (allele frequency exceeds 0.1%). PP3 is not met (SpliceAI delta = 0, no REVEL score available).

BA1 alone satisfies the Benign classification rule under both the León-Castillo custom POLE framework and generic ACMG/AMP 2015 combination rules.

Met · 3

BA1 Stand aloneThis variant is present at high frequency in gnomAD population databases. In gnomAD v2.1: overall AF=0.4166% (1169/280568 alleles), African/African American subpopulation AF=4.23% (1052/24896 alleles), grpmax FAF=4.01%, with 16 homozygotes observed. In gnomAD v4.1: overall AF=0.2185% (3498/1600686 alleles), African/African American subpopulation AF=4.17% (3108/74566 alleles), grpmax FAF=4.05%, with 54 homozygotes observed. The grpmax filtering allele frequency exceeds the BA1 threshold of >1% in both datasets, and the observation of multiple homozygotes confirms this is a common population polymorphism incompatible with a Mendelian disease-causing role. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: overall AF=0.4166%
  • African/African American AF=4.23%
  • grpmax FAF=4.01%
  • 16 homozygotes
  • gnomAD v4.1: overall AF=0.2185%
  • African/African American AF=4.17%
  • grpmax FAF=4.05%
  • 54 homozygotes
  • grpmax FAF exceeds 1% BA1 threshold by ~4-fold
  • Multiple homozygotes observed in both datasets — incompatible with a highly penetrant pathogenic role
Sources
gnomad_v2 ↗gnomad_v4 ↗
BP4 SupportingSpliceAI predicts no splicing impact for this intronic variant (max delta score = 0.00), indicating that the c.6330+19G>A substitution does not create or disrupt a splice site. In the absence of applicable missense prediction tools (REVEL and BayesDel not available for intronic variants), SpliceAI provides the primary computational evidence for this variant class, and its prediction of no splicing effect supports a benign interpretation. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.00 — no predicted donor gain/loss
  • no acceptor gain/loss
  • Variant is at intronic +19 position — SpliceAI is the most relevant in silico tool for this variant type
Sources
spliceai ↗
BP6 SupportingClinVar reports this variant as Benign (6 clinical laboratories: GeneDx, PreventionGenetics, ARUP Laboratories, KCCC/NGS Laboratory, Labcorp/Invitae, and Center for Genomic Medicine Rigshospitalet). Although review status is 'criteria provided, single submitter' and no expert panel review is recorded, the unanimous classification as Benign across multiple independent clinical laboratories provides supporting evidence for a benign interpretation. Details ▾Hide ▴
Evidence considered
  • ClinVar variation ID 380224: Benign
  • 6 clinical laboratories unanimously classify as Benign
  • Submitters include GeneDx
  • PreventionGenetics
  • ARUP
  • KCCC/NGS Lab
  • Labcorp/Invitae
  • Center for Genomic Medicine Rigshospitalet
Sources
clinvar ↗

Not met · 9 · evaluated, threshold not reached

PS3 No functional studies have been performed on this intronic variant. No publications report in vitro or in vivo functional data for NM_006231.4:c.6330+19G>A. Details ▾Hide ▴
Evidence considered
  • Literature review identified no functional studies for this variant
  • Three ClinVar-associated PMIDs (25741868
  • 28492532
  • 31275557) are methodology papers with no variant-specific functional data
PM2 PM2 requires absence from population databases or presence at extremely low frequency (<0.1%). This variant is common in gnomAD: v2.1 overall AF=0.4166% (1169/280568 alleles, 16 homozygotes); v4.1 overall AF=0.2185% (3498/1600686 alleles, 54 homozygotes). Both exceed the 0.1% threshold for PM2. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: AF=0.4166%
  • 1169/280568 alleles
  • 16 homozygotes
  • gnomAD v4.1: AF=0.2185%
  • 3498/1600686 alleles
  • 54 homozygotes
  • Frequency exceeds PM2 threshold of <0.1%
Sources
gnomad_v2 ↗gnomad_v4 ↗
PP1 No segregation data are available for this variant. PP1 requires cosegregation of the variant with disease in multiple affected family members. Details ▾Hide ▴
Evidence considered
  • No family segregation data in ClinVar or literature
PP3 SpliceAI predicts no splicing impact (max delta score = 0.00). REVEL and BayesDel scores are not available for this intronic variant. The custom POLE PP3 framework requires the variant to appear in Supplementary Table S2 or S3 with REVEL class 'likely disease causing' — this variant is absent from those tables. No computational evidence supports pathogenicity. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.00 — no predicted splice alteration
  • REVEL not available (intronic
  • no amino acid substitution)
  • BayesDel not available
  • HCI prior not available (gene not supported)
  • Variant absent from León-Castillo Supplementary Tables S2 and S3
Sources
spliceai ↗vcep_path_250_323_s003vcep_path_250_323_s004
PP4 No patient phenotype data specific to this variant are available. PP4 requires the patient's phenotype or family history to be highly specific for the disease associated with the gene. Details ▾Hide ▴
Evidence considered
  • No phenotype data reported for carriers of NM_006231.4:c.6330+19G>A
PP5 PP5 requires a reputable source to have classified the variant as pathogenic. ClinVar classifies this variant as Benign (6 clinical laboratories, variation ID 380224). No source classifies it as pathogenic. Details ▾Hide ▴
Evidence considered
  • ClinVar classification: Benign (6 clinical laboratories)
  • No expert panel or reputable source classifying as pathogenic
Sources
clinvar ↗
BS2 BS2 requires observation of the variant in a healthy adult individual in the homozygous state, or in trans with a pathogenic variant, with full penetrance expected at an early age for a dominant disorder. While multiple homozygotes in gnomAD are strong evidence captured by BA1, no published case reports document the specific clinical phenotype of homozygous carriers or trans configurations. BA1 already captures the population-level evidence. Details ▾Hide ▴
Evidence considered
  • 16 homozygotes in gnomAD v2.1
  • 54 in v4.1 strongly support benign classification via BA1
  • No published clinical case reports of homozygous carriers for BS2 attribution
Still missing
  • No published phenotypic data on homozygous carriers
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS3 No well-established functional studies have demonstrated no deleterious effect of this variant. BS3 requires a well-established assay showing no damaging effect on protein function or splicing. Details ▾Hide ▴
Evidence considered
  • No functional studies of any kind identified for this intronic variant
BS4 No segregation data are available demonstrating lack of cosegregation with disease. BS4 requires observation of the variant in multiple family members without the disease phenotype. Details ▾Hide ▴
Evidence considered
  • No family segregation data available for this variant
Not applicable · 14· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis is a deep intronic variant (c.6330+19G>A in intron 45). It does not fall into any null-variant bucket (nonsense, frameshift, or canonical ±1,2 splice consensus). SpliceAI max delta score is 0.00, confirming no predicted impact on splicing. The generic PVS1 framework is not applicable. Details ▾Hide ▴
Evidence considered
  • Variant class: deep intronic (+19)
  • not a canonical splice site variant
  • SpliceAI max delta = 0.00 — no predicted splicing impact
  • pvs1_variant_assessment.json confirms variant_bucket='other'
  • apply_generic_pvs1_framework=false
Sources
pvs1_generic_framework ↗pvs1_variant_assessmentspliceai ↗
PS1 N/APS1 applies when a different nucleotide change at the same position has been previously established as pathogenic. No known pathogenic variant exists at the c.6330+19 nucleotide position. This is an intronic substitution with no ClinVar or literature evidence of a pathogenic substitution at this exact position. Details ▾Hide ▴
Evidence considered
  • No pathogenic variant reported at c.6330+19 position in ClinVar or gnomAD
Sources
clinvar ↗
PS2 N/ANo de novo data available for this variant. PS2 requires a confirmed de novo observation in a patient with the disease and no family history. Details ▾Hide ▴
Evidence considered
  • No de novo reports in ClinVar or literature for NM_006231.4:c.6330+19G>A
PS4 N/AThe custom POLE framework PS4 rule is restricted to exact missense variants recurrent in both COSMIC and TCGA endometrial carcinoma cohorts with combined EC count ≥10 in the established pathogenic set highlighted by León-Castillo et al. 2020. NM_006231.4:c.6330+19G>A is an intronic variant, not a missense change, and is absent from the VCEP POLE supplementary tables. The generic PS4 (case-control or increased prevalence in affected individuals) also lacks supporting data. Details ▾Hide ▴
Evidence considered
  • Variant is intronic — not eligible for POLE custom PS4 (missense-only rule)
  • Not listed in León-Castillo et al. Supplementary Table S1 (recurrent variants)
  • No case-control or disease association data available
Sources
vcep_path_250_323vcep_path_250_323_s002
PM1 N/AThe custom POLE framework PM1 rules apply only to specific exonuclease-domain missense hotspot variants (P286R, V411L, S297F, A456P, S459F for PM1_Strong; F367S, L424I, M295R, P436R, M444K, D368Y for PM1_Moderate; A465V, L424V, T278M, A428T for PM1_Supporting). NM_006231.4:c.6330+19G>A is a deep intronic variant with no protein consequence and is not in a known functional domain hotspot. Generic PM1 (mutational hot spot) also does not apply as there is no pathogenic variation clustered at this intronic position. Details ▾Hide ▴
Evidence considered
  • Variant is intronic — not a missense change in the exonuclease domain
  • Not one of the established POLE hotspot residues
  • Variant not listed in León-Castillo et al. Supplementary Table S1
Sources
vcep_path_250_323vcep_path_250_323_s002
PM5 N/APM5 requires a different pathogenic missense change at the same amino acid residue. This is an intronic variant with no protein consequence (NP_006222.2:p.?). No same-residue comparator is possible. pm5_candidates.json confirms eligible_for_classic_pm5_search=false. Details ▾Hide ▴
Evidence considered
  • Intronic variant — no amino acid residue to compare
  • pm5_candidates.json: eligible_for_classic_pm5_search=false
Sources
pm5_candidates
PM6 N/ANo de novo observation reported for this variant. PM6 requires a confirmed de novo event with confirmed maternity and paternity. Details ▾Hide ▴
Evidence considered
  • No de novo reports in ClinVar or literature for NM_006231.4:c.6330+19G>A
PP2 N/APP2 applies to missense variants in a gene with a low rate of benign missense variation and where missense is a common pathogenic mechanism. NM_006231.4:c.6330+19G>A is an intronic variant, not a missense change. Details ▾Hide ▴
Evidence considered
  • Not a missense variant
BS1 N/ABA1 (stand-alone benign) has been met at a higher strength level based on grpmax filtering allele frequency >1%. BS1 (>0.3% overall) is superseded by BA1. Details ▾Hide ▴
Evidence considered
  • BA1 met — BS1 is superseded by the stronger stand-alone benign criterion
Sources
gnomad_v2 ↗gnomad_v4 ↗
BP1 N/ABP1 applies to missense variants in genes where a truncating (loss-of-function) mechanism is the primary cause of disease. NM_006231.4:c.6330+19G>A is a deep intronic variant, not a missense change. Details ▾Hide ▴
Evidence considered
  • Not a missense variant
BP2 N/ABP2 requires observation of the variant in trans with a known pathogenic variant in a gene for a fully penetrant dominant disorder, or in cis with a pathogenic variant in a recessive disorder. No such observations have been reported. Details ▾Hide ▴
Evidence considered
  • No reported observations in trans with a pathogenic POLE variant
BP5 N/ABP5 requires observation of the variant in a case with an alternate molecular basis for disease. No such case data are available for NM_006231.4:c.6330+19G>A. Details ▾Hide ▴
Evidence considered
  • No case reports of this variant in individuals with an alternate molecular diagnosis
BP7 N/ABP7 applies to synonymous (silent) variants for which splicing prediction algorithms predict no impact. NM_006231.4:c.6330+19G>A is a deep intronic variant, not a synonymous coding variant. Details ▾Hide ▴
Evidence considered
  • Not a synonymous variant — deep intronic at position +19
PS5 N/APS5 requires a reputable source (e.g., ClinGen expert panel) to have classified this variant as pathogenic, with evidence not independently verified. ClinVar classifies this variant as Benign, not Pathogenic. No expert panel has classified it as pathogenic. Details ▾Hide ▴
Evidence considered
  • ClinVar classification is Benign (6 clinical laboratories)
  • not Pathogenic
Sources
clinvar ↗

Identifiers

Gene
POLE
Transcript
NM_006231.4
Coding (HGVS c.)
NM_006231.4:c.6330+19G>A
Protein (HGVS p.)
NP_006222.2:p.?
GRCh38
chr12:132632296 C>T
GRCh37
chr12:133208882 C>T
ClinVar
380224

Gene diagram

Every interpreted variant in POLE, mapped onto the exon structure of NM_006231.4. Select a row to find it on the plot.

POLENM_006231.4
Fetching transcript structure from UCSC…
gnomAD v4.1 3,498 / 1,600,686 alleles AF 0.00219 · 54 homozygotes · FAF 0.0405
gnomAD v2.1 1,169 / 280,568 alleles AF 0.00417 · 16 homozygotes · FAF 0.0401
gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 0.0022 · 3498 / 1,600,686 alleles · 54 hom · FAF 0.04
African/African American3108 / 74,566 0.04249 hom
Admixed American163 / 59,906 0.0027
Remaining individuals167 / 61,974 0.00275 hom
Middle Eastern6 / 5,890 0.001
South Asian7 / 90,698 7.7e-05
European (non-Finnish)46 / 1,168,498 3.9e-05
Ashkenazi Jewish1 / 29,482 3.4e-05
0 alternate alleles recorded in 3 other groups: European (Finnish), Amish, East Asian.

gnomAD v2.1

AF 0.0042 · 1169 / 280,568 alleles · 16 hom · FAF 0.04
African/African American1052 / 24,896 0.04215 hom
Admixed American90 / 35,314 0.0025
Remaining individuals10 / 7,168 0.00141 hom
European (non-Finnish)14 / 127,806 0.00011
Ashkenazi Jewish1 / 10,280 9.7e-05
South Asian2 / 30,512 6.6e-05
0 alternate alleles recorded in 2 other groups: East Asian, European (Finnish).

gnomAD-Canada

AF not recorded · ? / ? alleles

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0.00218531; MAF= 0.21853%, 3498/1600686 alleles, homozygotes = 54) and has highest observed frequency in the African/African American population (AF= 0.0416812; MAF= 4.16812%, 3108/74566 alleles, homozygotes = 49); grpmax FAF= 0.0404589.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.00416655; MAF= 0.41665%, 1169/280568 alleles, homozygotes = 16) and has highest observed frequency in the African/African American population (AF= 0.0422558; MAF= 4.22558%, 1052/24896 alleles, homozygotes = 15); grpmax FAF= 0.0401049.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.0024445893089960887, 45/18408 alleles, homozygotes = 1).

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

Pangolin splice lossmagnitude shown
-0.000
Pangolin splice gain
0.000

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP4 SupportingSpliceAI predicts no splicing impact for this intronic variant (max delta score = 0.00), indicating that the c.6330+19G>A substitution does not create or disrupt a splice site. In the absence of applicable missense prediction tools (REVEL and BayesDel not available for intronic variants), SpliceAI provides the primary computational evidence for this variant class, and its prediction of no splicing effect supports a benign interpretation. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.00 — no predicted donor gain/loss
  • no acceptor gain/loss
  • Variant is at intronic +19 position — SpliceAI is the most relevant in silico tool for this variant type
Sources
spliceai ↗
PP3 SpliceAI predicts no splicing impact (max delta score = 0.00). REVEL and BayesDel scores are not available for this intronic variant. The custom POLE PP3 framework requires the variant to appear in Supplementary Table S2 or S3 with REVEL class 'likely disease causing' — this variant is absent from those tables. No computational evidence supports pathogenicity. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.00 — no predicted splice alteration
  • REVEL not available (intronic
  • no amino acid substitution)
  • BayesDel not available
  • HCI prior not available (gene not supported)
  • Variant absent from León-Castillo Supplementary Tables S2 and S3
Sources
spliceai ↗vcep_path_250_323_s003vcep_path_250_323_s004
BP7 N/ABP7 applies to synonymous (silent) variants for which splicing prediction algorithms predict no impact. NM_006231.4:c.6330+19G>A is a deep intronic variant, not a synonymous coding variant. Details ▾Hide ▴
Evidence considered
  • Not a synonymous variant — deep intronic at position +19

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

3 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.

Recorded publications

  • Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
    Richards S et al. · 2015
    No paper-specific finding is recorded.
    PMID 25741868 ↗
  • PMID 28492532
    No paper-specific finding is recorded.
    PMID 28492532 ↗
  • Pan-cancer repository of validated natural and cryptic mRNA splicing mutations.
    Shirley BC et al. · 2018
    No paper-specific finding is recorded.
    PMID 31275557 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 3,498 / 1,600,686 recorded alleles Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗
ClinVar 6 Benign Open source ↗
COSMIC Captured COSMIC source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0.00218531; MAF= 0.21853%, 3498/1600686 alleles, homozygotes = 54) and has highest observed frequency in the African/African American population (AF= 0.0416812; MAF= 4.16812%, 3108/74566 alleles, homozygotes = 49); grpmax FAF= 0.0404589.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.00416655; MAF= 0.41665%, 1169/280568 alleles, homozygotes = 16) and has highest observed frequency in the African/African American population (AF= 0.0422558; MAF= 4.22558%, 1052/24896 alleles, homozygotes = 15); grpmax FAF= 0.0401049.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.0024445893089960887, 45/18408 alleles, homozygotes = 1).

ClinVar

This variant has been reported in ClinVar as Benign (6 clinical laboratories). (ClinVarID = 380224)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

Somatic

This variant has not previously been reported in somatic cancers (COSMIC).