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POLEc.1474-9C>TLikely benign
Print report
Variant interpretation report

POLE c.1474-9C>T, p.?

NM_006231.4:c.1474-9C>T NP_006222.2:p.? View identifiers
Classification
Likely benign

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.

Likely benign.A likely 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: 1 Benign evidence criteria: 2
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting

This variant is present at extremely low allele frequency in population databases: gnomAD v2.1 AF = 4.10e-06 (1/244,126 alleles, 0 homozygotes) and gnomAD v4.1 AF = 6.20e-07 (1/1,611,808 alleles, 0 homozygotes). Both frequencies are well below the 0.1% PM2 threshold. The variant is absent from gnomAD-Canada v1.0.

Benign criteria applied · 2
BP4Supporting
BP4 · supporting

SpliceAI predicts no significant splice impact for this intronic substitution (max delta score = 0.01), suggesting the variant is unlikely to disrupt normal splicing of POLE. The custom León-Castillo BP4 rule applies only to missense variants in Supplementary Tables S2/S3 and is not triggered here; under generic BP4 assessment, computational evidence supports a neutral effect.

BP6Supporting
BP6 · supporting

This variant has been classified as Likely benign by a clinical diagnostic laboratory (Labcorp Genetics, formerly Invitae; ClinVar SCV004525736, VariationID 2897960) with criteria provided. The submitter is a reputable clinical testing laboratory.

Recorded classification: Likely benign

The custom León-Castillo et al. 2020 POLE framework was used as the primary classification framework. Only supporting-strength criteria are met: one pathogenic (PM2_Supporting) and two benign (BP4_Supporting, BP6_Supporting). Under the framework's likely_benign combination rules, >=2 Supporting benign criteria are sufficient for a Likely Benign classification.

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
1 / 1,611,808 alleles

gnomAD v4.1: 1 / 1,611,808 alleles. Recorded AF 6.20421e-07. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.09625e-06; MAF= 0.00041%, 1/244126 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 5.6035e-05; MAF= 0.00560%, 1/17846 alleles, homozygotes = 0).

Applied · PM2 →
gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗
SpliceAI score
0.010 maximum delta

Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4 → SpliceAI ↗
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.

29 criteria with recorded statuses: 3 met · 10 not met · 7 not assessed · 9 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM3PM4PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

NM_006231.4:c.1474-9C>T is an intronic substitution in POLE located 9 bases upstream of exon 14. SpliceAI predicts no significant splicing impact (max delta score = 0.01), indicating the variant is unlikely to alter normal splicing.

This variant is extremely rare in population databases, with an allele frequency of 4.10e-06 in gnomAD v2.1 (1/244,126 alleles) and 6.20e-07 in gnomAD v4.1 (1/1,611,808 alleles), both meeting the PM2_Supporting threshold for absence from population databases.

ClinVar classifies this variant as Likely benign (VariationID 2897960, Labcorp Genetics, criteria provided, single submitter), supporting benign interpretation under BP6_Supporting.

SpliceAI predicts no significant splice impact (max delta score = 0.01), consistent with a neutral computational assessment under BP4_Supporting.

No pathogenic evidence criteria are met. The custom León-Castillo PM1 and PS4 rules are missense-specific and do not apply to this intronic substitution. The variant is absent from COSMIC and the León-Castillo supplementary tables. No de novo observations, functional studies, or segregation data are available.

Applying the custom León-Castillo framework with generic ACMG/AMP 2015 fallback: the variant accrues one pathogenic supporting criterion (PM2_Supporting) and two benign supporting criteria (BP4_Supporting, BP6_Supporting). Under the likely_benign combination rules of the framework, two supporting benign criteria are sufficient for a classification of Likely benign. This classification is consistent with the existing ClinVar classification.

Met · 3

PM2 SupportingThis variant is present at extremely low allele frequency in population databases: gnomAD v2.1 AF = 4.10e-06 (1/244,126 alleles, 0 homozygotes) and gnomAD v4.1 AF = 6.20e-07 (1/1,611,808 alleles, 0 homozygotes). Both frequencies are well below the 0.1% PM2 threshold. The variant is absent from gnomAD-Canada v1.0. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: 1/244
  • 126 alleles (AF=4.10e-06)
  • 0 homozygotes
  • gnomAD v4.1: 1/1
  • 611
  • 808 alleles (AF=6.20e-07)
  • Highest subpopulation frequency: East Asian
  • v2.1 AF=5.60e-05 (1/17
  • 846)
  • Absent from gnomAD-Canada v1.0
Sources
gnomad_v2 ↗gnomad_v4 ↗
BP4 SupportingSpliceAI predicts no significant splice impact for this intronic substitution (max delta score = 0.01), suggesting the variant is unlikely to disrupt normal splicing of POLE. The custom León-Castillo BP4 rule applies only to missense variants in Supplementary Tables S2/S3 and is not triggered here; under generic BP4 assessment, computational evidence supports a neutral effect. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.01 (well below commonly used thresholds of 0.1-0.2 for splice effect prediction)
  • REVEL
  • BayesDel not applicable to intronic variants
Sources
spliceai ↗
BP6 SupportingThis variant has been classified as Likely benign by a clinical diagnostic laboratory (Labcorp Genetics, formerly Invitae; ClinVar SCV004525736, VariationID 2897960) with criteria provided. The submitter is a reputable clinical testing laboratory. Details ▾Hide ▴
Evidence considered
  • ClinVar Likely benign classification from Labcorp Genetics (SCV004525736)
  • Criteria provided
  • single submitter
  • Reputable clinical diagnostic laboratory
Still missing
  • Single submitter only
  • no expert panel review
Sources
clinvar ↗

Not met · 10 · evaluated, threshold not reached

PS2 No de novo observation of NM_006231.4:c.1474-9C>T has been reported in the literature or clinical databases. PS2 requires a confirmed de novo occurrence with maternity and paternity confirmed. Details ▾Hide ▴
Evidence considered
  • No de novo reports identified in ClinVar
  • literature search
  • or case evidence
Still missing
  • No de novo testing data available for this variant
PS4 The custom León-Castillo PS4 rule applies only to missense variants recurrent in COSMIC and TCGA endometrial carcinoma cohorts with combined EC count ≥10. NM_006231.4:c.1474-9C>T is an intronic substitution, not assessed in the León-Castillo supplementary tables, and is absent from COSMIC. No germline case-control studies have been identified that report this variant in affected versus unaffected individuals. Details ▾Hide ▴
Evidence considered
  • Absent from COSMIC
  • Not present in León-Castillo Supplementary Table S1 (recurrent POLE variants)
  • Custom PS4 rule is missense-specific
  • No germline case-control data identified
Still missing
  • No cohort or case-control studies reporting prevalence in affected individuals
Sources
vcep_path_250_323_s002
PM1 The custom León-Castillo PM1 rules apply only to specific missense variants in the exonuclease domain (five established hotspots at PM1_Strong, specific recurrent variants at PM1_Moderate, and specific uncertain-tier variants at PM1_Supporting). NM_006231.4:c.1474-9C>T is an intronic substitution, not a missense variant, and does not appear in the León-Castillo supplementary tables. Although the variant is located in intron 13 adjacent to exon 14 (which encodes part of the exonuclease domain), SpliceAI predicts no significant splicing impact (max delta 0.01), so there is no evidence this substitution disrupts a critical functional domain. Details ▾Hide ▴
Evidence considered
  • Not one of the five established hotspot missense variants
  • Not a missense variant
  • custom PM1 rules are missense-specific
  • SpliceAI max delta = 0.01
  • no predicted disruption of exon 14 splicing
  • Not present in Supplementary Table S1
Still missing
  • No direct functional evidence that this intronic change affects exonuclease domain function
Sources
spliceai ↗vcep_path_250_323_s002
PM6 No de novo observation of NM_006231.4:c.1474-9C>T has been reported in the literature or clinical databases. PM6 requires a de novo observation without confirmation of maternity and paternity; no such report exists for this variant. Details ▾Hide ▴
Evidence considered
  • No de novo reports identified in any data source
Still missing
  • No de novo testing data available
PP3 The custom León-Castillo PP3 rule applies only to missense variants present in Supplementary Tables S2 or S3 with REVEL class 'likely disease causing' and ≤1 benign in silico result. NM_006231.4:c.1474-9C>T is an intronic substitution not found in these tables. Under generic in silico assessment: SpliceAI predicts no significant splicing effect (max delta 0.01); REVEL, BayesDel, and HCI prior scores are not available for this intronic variant. No computational evidence supports a pathogenic effect. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.01 (no predicted splice impact)
  • Not present in Supplementary Tables S2 or S3
  • REVEL score not available (intronic variant)
  • BayesDel score not available
  • HCI prior not available (POLE not supported)
Sources
spliceai ↗vcep_path_250_323_s003vcep_path_250_323_s004
PP5 ClinVar classifies this variant as Likely benign (VariationID 2897960, Labcorp Genetics, criteria provided, single submitter). PP5 requires a reputable source to have independently classified the variant as pathogenic. The ClinVar submission cites PMID:28492532 (Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria), which is a general methodology paper and does not contain variant-specific evidence for NM_006231.4:c.1474-9C>T. No full-text is available for this PMID, but its title and known content confirm it is a framework paper, not a case report. Details ▾Hide ▴
Evidence considered
  • ClinVar classification: Likely benign (not pathogenic)
  • PMID:28492532 is a methods paper
  • not a variant-specific case report
  • No reputable source has classified this variant as pathogenic
Sources
clinvar ↗28492532
BA1 The allele frequency in gnomAD v2.1 (AF = 4.10e-06, 0.0004%) and v4.1 (AF = 6.20e-07, 0.00006%) is far below the 1% BA1 threshold. This criterion is not met. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 AF = 0.0004% (well below 1%)
  • gnomAD v4.1 AF = 0.00006% (well below 1%)
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS1 The allele frequency in gnomAD v2.1 (AF = 4.10e-06, 0.0004%) is far below the 0.3% BS1 threshold. The highest subpopulation frequency is in East Asians at 0.0056% (v2.1), also well below the threshold. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 overall AF = 0.0004% (below 0.3%)
  • Highest subpopulation AF (East Asian
  • v2.1) = 0.0056% (below 0.3%)
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS2 The variant is not observed in a homozygous state in gnomAD (0 homozygotes in both v2.1 and v4.1). No systematic evidence of observation in healthy adults independent of population databases has been identified. BS2 requires observation in a healthy adult individual for a recessive disorder, or observation in trans with a pathogenic variant, or homozygous observation in a dominant disorder with full penetrance expected early in life. Details ▾Hide ▴
Evidence considered
  • 0 homozygotes in gnomAD v2.1 and v4.1
  • Only 1 heterozygous observation across both gnomAD versions
  • No reports of this variant in healthy adults
Still missing
  • No curated healthy control cohort data
Sources
gnomad_v2 ↗gnomad_v4 ↗
PS5 ClinVar classifies this variant as Likely benign (VariationID 2897960, 1 clinical laboratory submitter: Labcorp Genetics). PS5 requires a reputable source to have independently classified the variant as pathogenic; the current ClinVar classification contradicts this. The ClinVar submission cites PMID:28492532 (Sherloc methods paper), which does not contain variant-specific evidence for NM_006231.4:c.1474-9C>T. Details ▾Hide ▴
Evidence considered
  • ClinVar classification: Likely benign
  • criteria provided
  • single submitter (SCV004525736)
  • No reputable source has independently classified this variant as pathogenic
Sources
clinvar ↗28492532

Not assessed · 7 · no assessment recorded

PS3 No functional studies (e.g., RNA splicing assays, minigene constructs, polymerase activity assays) have been identified that evaluate the functional impact of NM_006231.4:c.1474-9C>T. SpliceAI predicts no splicing effect, but direct experimental validation is absent. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.01
  • predicting no splicing alteration
  • but no confirmatory in vitro functional data exist
Still missing
  • No RNA-based functional studies (RT-PCR
  • minigene splicing assay) available
  • No functional complementation or enzymatic assay data
Sources
spliceai ↗
PP1 No co-segregation data are available for NM_006231.4:c.1474-9C>T. PP1 requires evidence of co-segregation with disease in multiple affected family members. Details ▾Hide ▴
Evidence considered
  • No family studies or segregation data identified for this variant
Still missing
  • No segregation analysis in affected families
  • No pedigree data available
PP4 No phenotype or clinical data specifically associated with NM_006231.4:c.1474-9C>T have been identified. PP4 requires that the variant is found in a patient whose phenotype or family history is highly specific for the gene/disease. Details ▾Hide ▴
Evidence considered
  • No patient phenotype data available for this variant
Still missing
  • No clinical phenotype information available
  • No family history data
BS3 No functional studies (e.g., RNA splicing assays, minigene constructs, enzymatic activity assays) assessing the impact of NM_006231.4:c.1474-9C>T have been identified. BS3 requires well-established in vitro or in vivo functional studies demonstrating no damaging effect on protein function or splicing. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.01
  • predicting no splicing alteration
  • but computational prediction alone is insufficient for BS3
Still missing
  • No direct RNA-based functional studies
  • No protein-level functional assays
Sources
spliceai ↗
BS4 No segregation data are available for NM_006231.4:c.1474-9C>T. BS4 requires lack of co-segregation with disease in affected family members. Details ▾Hide ▴
Evidence considered
  • No segregation or family studies available for this variant
Still missing
  • No family studies or pedigree data
  • No segregation analysis
BP2 No observations of NM_006231.4:c.1474-9C>T in trans with a known pathogenic POLE variant have been reported. BP2 requires observation in trans with a pathogenic variant in a gene associated with a recessive disorder, or observation in cis with a pathogenic variant in any inheritance pattern. Details ▾Hide ▴
Evidence considered
  • No in trans or in cis observations with pathogenic variants reported
Still missing
  • No phase data available
  • No co-occurrence data with other POLE variants
BP5 No observations of NM_006231.4:c.1474-9C>T in cases with an alternate molecular cause for disease have been identified. BP5 requires that the variant is found in a case with an alternate molecular basis for disease. Details ▾Hide ▴
Evidence considered
  • No cases with alternate molecular diagnosis reported
Still missing
  • No data on co-occurrence with other molecular diagnoses
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis intronic variant (c.1474-9C>T) does not fall into the PVS1 null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants. SpliceAI predicts no significant splicing effect (max delta 0.01). The generic PVS1 framework (PMC6185798) does not apply to this variant class. Details ▾Hide ▴
Evidence considered
  • Variation is an intronic substitution at c.1474-9
  • not a canonical splice site
  • SpliceAI max delta score = 0.01
  • indicating no predicted splicing impact
  • PVS1 variant assessment explicitly assigns bucket 'other' and recommends against applying generic PVS1 framework
Sources
spliceai ↗pvs1_variant_assessmentpvs1_gene_context
PS1 N/APS1 requires a known pathogenic variant with the same amino acid change as the variant under assessment. NM_006231.4:c.1474-9C>T is an intronic substitution with unknown protein consequence (p.?); no amino acid change is defined. Details ▾Hide ▴
Evidence considered
  • Intronic variant with no defined protein consequence
  • PS1 is applicable only to missense variants with a known pathogenic comparator at the same residue
PM3 N/APM3 applies to variants detected in trans with a pathogenic variant in recessive disorders. POLE is associated with autosomal dominant polymerase proofreading-associated polyposis (PPAP), and recessive inheritance is not established. Details ▾Hide ▴
Evidence considered
  • POLE-associated disease is autosomal dominant
  • PM3 is for recessive disorders
PM4 N/APM4 applies to protein-length altering in-frame insertions, deletions, or stop-loss variants. NM_006231.4:c.1474-9C>T is an intronic single-nucleotide substitution that does not alter protein length through these mechanisms. Details ▾Hide ▴
Evidence considered
  • Single-nucleotide intronic substitution
  • not an in-frame indel or stop-loss
PM5 N/APM5 requires a known pathogenic missense change at the same amino acid residue as the variant under assessment. NM_006231.4:c.1474-9C>T is an intronic substitution with unknown protein consequence (p.?); no amino acid residue can be assigned. Details ▾Hide ▴
Evidence considered
  • Intronic variant with no protein residue assignment
  • PM5 candidates collection returned no eligible comparators
PP2 N/APP2 applies to missense variants in genes where missense variants are a common mechanism of disease and benign missense variation is low. NM_006231.4:c.1474-9C>T is an intronic substitution, not a missense variant. Details ▾Hide ▴
Evidence considered
  • Intronic substitution
  • not a missense variant
BP1 N/ABP1 applies to missense variants in genes where truncating variants are the primary known disease mechanism. NM_006231.4:c.1474-9C>T is an intronic substitution, not a missense variant. Details ▾Hide ▴
Evidence considered
  • Intronic substitution
  • not a missense variant
BP3 N/ABP3 applies to in-frame insertions or deletions in repetitive regions without known function. This is a single-nucleotide intronic substitution, not an in-frame indel. Details ▾Hide ▴
Evidence considered
  • Not an in-frame insertion or deletion
BP7 N/ABP7 applies to synonymous (silent) coding variants with no predicted splice impact. NM_006231.4:c.1474-9C>T is an intronic substitution located 9 bases upstream of exon 14, not a synonymous coding variant. Details ▾Hide ▴
Evidence considered
  • Intronic variant
  • not a synonymous coding variant

Identifiers

Gene
POLE
Transcript
NM_006231.4
Coding (HGVS c.)
NM_006231.4:c.1474-9C>T
Protein (HGVS p.)
NP_006222.2:p.?
GRCh38
chr12:132672848 G>A
GRCh37
chr12:133249434 G>A
ClinVar
2897960

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 1 / 1,611,808 alleles AF 6.2e-07 · 0 homozygotes
gnomAD v2.1 1 / 244,126 alleles AF 4.1e-06 · 0 homozygotes
gnomAD-Canada v1.0 0 / 0 alleles AF 0 · 0 homozygotes · FAF 0

By genetic ancestry

gnomAD v4.1

AF 6.2e-07 · 1 / 1,611,808 alleles · 0 hom
East Asian1 / 44,800 2.2e-05
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish).

gnomAD v2.1

AF 4.1e-06 · 1 / 244,126 alleles · 0 hom
East Asian1 / 17,846 5.6e-05
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.

gnomAD-Canada

AF 0 · 0 / 0 alleles · 0 hom

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 6.20421e-07; MAF= 0.00006%, 1/1611808 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.23214e-05; MAF= 0.00223%, 1/44800 alleles, homozygotes = 0).

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.09625e-06; MAF= 0.00041%, 1/244126 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 5.6035e-05; MAF= 0.00560%, 1/17846 alleles, homozygotes = 0).

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

SpliceAI acceptor lossat -9 bp
0.000
SpliceAI acceptor gainat +9 bp
0.010
SpliceAI donor lossat -268 bp
0.000
SpliceAI donor gainat -221 bp
0.000
Pangolin splice lossmagnitude shown
-0.020
Pangolin splice gain
0.010

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP4 SupportingSpliceAI predicts no significant splice impact for this intronic substitution (max delta score = 0.01), suggesting the variant is unlikely to disrupt normal splicing of POLE. The custom León-Castillo BP4 rule applies only to missense variants in Supplementary Tables S2/S3 and is not triggered here; under generic BP4 assessment, computational evidence supports a neutral effect. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.01 (well below commonly used thresholds of 0.1-0.2 for splice effect prediction)
  • REVEL
  • BayesDel not applicable to intronic variants
Sources
spliceai ↗
PP3 The custom León-Castillo PP3 rule applies only to missense variants present in Supplementary Tables S2 or S3 with REVEL class 'likely disease causing' and ≤1 benign in silico result. NM_006231.4:c.1474-9C>T is an intronic substitution not found in these tables. Under generic in silico assessment: SpliceAI predicts no significant splicing effect (max delta 0.01); REVEL, BayesDel, and HCI prior scores are not available for this intronic variant. No computational evidence supports a pathogenic effect. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.01 (no predicted splice impact)
  • Not present in Supplementary Tables S2 or S3
  • REVEL score not available (intronic variant)
  • BayesDel score not available
  • HCI prior not available (POLE not supported)
Sources
spliceai ↗vcep_path_250_323_s003vcep_path_250_323_s004
BP7 N/ABP7 applies to synonymous (silent) coding variants with no predicted splice impact. NM_006231.4:c.1474-9C>T is an intronic substitution located 9 bases upstream of exon 14, not a synonymous coding variant. Details ▾Hide ▴
Evidence considered
  • Intronic variant
  • not a synonymous coding variant

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).

1 paper record 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

  • Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.
    Nykamp K et al. · 2017
    No paper-specific finding is recorded.
    PMID 28492532 ↗

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

gnomAD v4.1 1 / 1,611,808 recorded alleles Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.010 Open source ↗
ClinVar 1 Likely 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= 6.20421e-07; MAF= 0.00006%, 1/1611808 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.23214e-05; MAF= 0.00223%, 1/44800 alleles, homozygotes = 0).

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.09625e-06; MAF= 0.00041%, 1/244126 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 5.6035e-05; MAF= 0.00560%, 1/17846 alleles, homozygotes = 0).

ClinVar

This variant has been reported in ClinVar as Likely benign (1 clinical laboratory). (ClinVarID = 2897960)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).

Somatic

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