Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000038.6(APC):c.1635G>A (p.Ala545=)

CA005411

42239 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 8ebd9d7f-d1a0-47af-9174-119032365842

HGVS expressions

NM_000038.6:c.1635G>A

NM_000038.6(APC):c.1635G>A (p.Ala545=)

NC_000005.10:g.112828864G>A

CM000667.2:g.112828864G>A

NC_000005.9:g.112164561G>A

CM000667.1:g.112164561G>A

NC_000005.8:g.112192460G>A

NG_008481.4:g.141344G>A

ENST00000257430.9:c.1635G>A

ENST00000257430.8:c.1635G>A

ENST00000502371.2:n.97-6087G>A

ENST00000504915.2:n.324G>A

ENST00000505084.1:n.122G>A

ENST00000507379.5:c.1581G>A

ENST00000508376.6:c.1635G>A

ENST00000508624.5:c.*957G>A

ENST00000512211.6:c.1635G>A

ENST00000520401.1:n.122G>A

NM_000038.5:c.1635G>A

NM_001127510.2:c.1635G>A

NM_001127511.2:c.1581G>A

NM_001354895.1:c.1635G>A

NM_001354896.1:c.1689G>A

NM_001354897.1:c.1665G>A

NM_001354898.1:c.1560G>A

NM_001354899.1:c.1551G>A

NM_001354900.1:c.1512G>A

NM_001354901.1:c.1458G>A

NM_001354902.1:c.1362G>A

NM_001354903.1:c.1332G>A

NM_001354904.1:c.1257G>A

NM_001354905.1:c.1155G>A

NM_001354906.1:c.786G>A

NM_001127510.3:c.1635G>A

NM_001127511.3:c.1581G>A

NM_001354895.2:c.1635G>A

NM_001354896.2:c.1689G>A

NM_001354897.2:c.1665G>A

NM_001354898.2:c.1560G>A

NM_001354899.2:c.1551G>A

NM_001354900.2:c.1512G>A

NM_001354901.2:c.1458G>A

NM_001354902.2:c.1362G>A

NM_001354903.2:c.1332G>A

NM_001354904.2:c.1257G>A

NM_001354905.2:c.1155G>A

NM_001354906.2:c.786G>A

Benign

BA1 BP4 BP7

Evidence Links 0

Expert Panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

The c.1635G>A (p.Ala545=) variant is a synonymous (silent) variant that is not predicted to impact splicing (BP4, BP7). The highest population minor allele frequency in gnomAD v2.1.1 is 0.82 (15756 in 19198 alleles) in the East Asian population, which is higher than the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (HCCP VCEP) threshold (≥ 0.001) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as Benign for FAP based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: BA1, BP4, and BP7. (VCEP specifications version 1; date of approval: 12/12/2022).

BA1

The highest population minor allele frequency in gnomAD v2.1.1 is 0.82 (15756 in 19198 alleles) in the East Asian population, which is higher than the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP threshold (≥ 0.001) for BA1, and therefore meets this criterion (BA1).

BP4

The results from ≥2 in silico splicing predictors (SpliceAI, MaxEntScan, VarSeak) support that this variant does not affect splicing (BP4).

BP7

The c.1635G>A (p.Ala545=) variant (NM_000038.6) is a synonymous (silent) variant that is not predicted by SpliceAI, MaxEntScan, and varSEAK to impact splicing (BP4, BP7).

Approved on: 2023-02-19

Published on: 2023-03-14

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