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.1487C>T (p.Thr496Ile)

CA16024566

482257 (ClinVar)

Gene: APC
Condition: familial adenomatous polyposis 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 5a4f6d5b-488b-4358-9acc-b50cbd24728b
Approved on: 2023-02-19
Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.1487C>T
NM_000038.6(APC):c.1487C>T (p.Thr496Ile)
NC_000005.10:g.112827186C>T
CM000667.2:g.112827186C>T
NC_000005.9:g.112162883C>T
CM000667.1:g.112162883C>T
NC_000005.8:g.112190782C>T
NG_008481.4:g.139666C>T
ENST00000257430.9:c.1487C>T
ENST00000257430.8:c.1487C>T
ENST00000502371.2:n.96+5195C>T
ENST00000504915.2:n.176C>T
ENST00000507379.5:c.1433C>T
ENST00000508376.6:c.1487C>T
ENST00000508624.5:c.*809C>T
ENST00000512211.6:c.1487C>T
NM_000038.5:c.1487C>T
NM_001127510.2:c.1487C>T
NM_001127511.2:c.1433C>T
NM_001354895.1:c.1487C>T
NM_001354896.1:c.1541C>T
NM_001354897.1:c.1517C>T
NM_001354898.1:c.1412C>T
NM_001354899.1:c.1403C>T
NM_001354900.1:c.1364C>T
NM_001354901.1:c.1310C>T
NM_001354902.1:c.1214C>T
NM_001354903.1:c.1184C>T
NM_001354904.1:c.1109C>T
NM_001354905.1:c.1007C>T
NM_001354906.1:c.638C>T
NM_001127510.3:c.1487C>T
NM_001127511.3:c.1433C>T
NM_001354895.2:c.1487C>T
NM_001354896.2:c.1541C>T
NM_001354897.2:c.1517C>T
NM_001354898.2:c.1412C>T
NM_001354899.2:c.1403C>T
NM_001354900.2:c.1364C>T
NM_001354901.2:c.1310C>T
NM_001354902.2:c.1214C>T
NM_001354903.2:c.1184C>T
NM_001354904.2:c.1109C>T
NM_001354905.2:c.1007C>T
NM_001354906.2:c.638C>T
More

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"
Met criteria codes 3
BS2 BP1 PM2_Supporting
Not Met criteria codes 15
PS2 PS4 PS3 PS1 PP4 PP1 PM6 PM3 PM1 PM5 BS4 BS3 BP5 BP2 BP4

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.1487C>T variant in APC is a missense variant predicted to cause substitution of threonine by isoleucine at amino acid 496 (p.Thr496Ile). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). APC is defined by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (HCCP VCEP) as a gene for which primarily truncating variants are known to cause disease (BP1). This variant has been observed in a heterozygous state in 18 unrelated healthy adult individuals worth ≥ 10 healthy individual points in total (BS2; Ambry Genetics, Invitae, and GeneDX internal data). In summary, this variant meets the criteria to be classified as Likely Benign for FAP based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: BS2 and BP1 (VCEP specifications version 1.0, date of approval: 12/12/2022).
Met criteria codes
BS2
This variant has been observed in heterozygous state in 18 healthy unrelated adult individuals worth ≥ 10 healthy individual points in total (BS2; Ambry Genetics, Invitae, GeneDX internal data).
BP1
APC is defined by the ClinGen APC VCEP as a gene for which primarily truncating variants are known to cause disease (BP1).
PM2_Supporting
This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
SpliceAI predicts no impact on splicing (DS scores all 0). No MaxEntScan change.
Curation History
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