Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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Variant: NM_000038.6(APC):c.1549-13A>T

CA005295

140764 (ClinVar)

Gene: APC
Condition: familial adenomatous polyposis 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 3112af48-6d9c-4c40-b4e6-0b697b0b03e8
Approved on: 2023-02-19
Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.1549-13A>T
NM_000038.6(APC):c.1549-13A>T
NC_000005.10:g.112827916A>T
CM000667.2:g.112827916A>T
NC_000005.9:g.112163613A>T
CM000667.1:g.112163613A>T
NC_000005.8:g.112191512A>T
NG_008481.4:g.140396A>T
ENST00000257430.9:c.1549-13A>T
ENST00000257430.8:c.1549-13A>T
ENST00000502371.2:n.96+5925A>T
ENST00000504915.2:n.238-13A>T
ENST00000505084.1:n.36-13A>T
ENST00000507379.5:c.1495-13A>T
ENST00000508376.6:c.1549-13A>T
ENST00000508624.5:c.*871-13A>T
ENST00000512211.6:c.1549-13A>T
ENST00000520401.1:n.36-13A>T
NM_000038.5:c.1549-13A>T
NM_001127510.2:c.1549-13A>T
NM_001127511.2:c.1495-13A>T
NM_001354895.1:c.1549-13A>T
NM_001354896.1:c.1603-13A>T
NM_001354897.1:c.1579-13A>T
NM_001354898.1:c.1474-13A>T
NM_001354899.1:c.1465-13A>T
NM_001354900.1:c.1426-13A>T
NM_001354901.1:c.1372-13A>T
NM_001354902.1:c.1276-13A>T
NM_001354903.1:c.1246-13A>T
NM_001354904.1:c.1171-13A>T
NM_001354905.1:c.1069-13A>T
NM_001354906.1:c.700-13A>T
NM_001127510.3:c.1549-13A>T
NM_001127511.3:c.1495-13A>T
NM_001354895.2:c.1549-13A>T
NM_001354896.2:c.1603-13A>T
NM_001354897.2:c.1579-13A>T
NM_001354898.2:c.1474-13A>T
NM_001354899.2:c.1465-13A>T
NM_001354900.2:c.1426-13A>T
NM_001354901.2:c.1372-13A>T
NM_001354902.2:c.1276-13A>T
NM_001354903.2:c.1246-13A>T
NM_001354904.2:c.1171-13A>T
NM_001354905.2:c.1069-13A>T
NM_001354906.2:c.700-13A>T
More

Benign

Met criteria codes 4
BS2 BS3 BS1 BP4
Not Met criteria codes 1
BP7

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP
The c.1549-13A>T variant in APC is an intronic variant which is located 13 nucleotides upstream of exon 13. This variant has been observed in 10 individuals worth 10 healthy individual points (Ambry internal data). The highest population minor allele frequency in the non-cancer cohort of gnomAD v2.1.1 is 0.003915% in the non-Finnish European population, which is higher than the ClinGen APC VCEP threshold (0.001%) for BS1, and therefore meets this criterion (BS1). RT-PCR demonstrated no impact of the variant on splicing with evidence of biallelic expression (BS3, Ambry internal data). The results from ≥2 in silico splicing predictors (SpliceAI, MaxEntScan, VarSeak) support that this variant does not affect splicing (BP4). In summary, this variant is classified as Benign for autosomal dominant familial adenomatous polyposis as specified by the InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP. Criteria applied: BS1, BS2, BS3, BP4 (Specification Version 1.0, date of approval: 10/12/2022).
Met criteria codes
BS2
This variant has been observed 10 individuals worth 10 healthy individual points (BS2; Ambry internal data).
BS3
RT-PCR demonstrated no impact of the variant on splicing with evidence of biallelic expression (BS3, Ambry Internal data). In detail: RTPCRSeq, high coverage, no aberrant splicing. Allele skewing in neighbouring exon shows both alleles present in WT RNA reads.
BS1
The highest population minor allele frequency in the non-cancer cohort of gnomAD v2.1.1 is 0.003915% in the non-Finnish European population, which is higher than the ClinGen APC VCEP threshold (0.001%) for BS1, and therefore meets this criterion (BS1).
BP4
The results from ≥2 in silico splicing predictors (SpliceAI, MaxEntScan, VarSeak) support that this variant does not affect splicing (BP4).
Not Met criteria codes
BP7
Variant is proximal to the -21 splice acceptor site position threshold.
Curation History
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