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]

Variant: NM_000350.3(ABCA4):c.454C>T (p.Arg152Ter)

CA227213

99300 (ClinVar)

Gene: ABCA4 (HGNC:24)

Condition: ABCA4-related retinopathy (MONDO:0800406)

Inheritance Mode: Autosomal recessive inheritance

UUID: 44ec14d3-b4bf-4980-8ea9-82865842b350

Approved on: 2025-12-05

Published on: 2025-12-23

HGVS expressions

NM_000350.3(ABCA4):c.454C>T (p.Arg152Ter)

NM_000350.3:c.454C>T

NC_000001.11:g.94103131G>A

CM000663.2:g.94103131G>A

NC_000001.10:g.94568687G>A

CM000663.1:g.94568687G>A

NC_000001.9:g.94341275G>A

NG_009073.1:g.23019C>T

ENST00000370225.4:c.454C>T

ENST00000649773.1:c.454C>T

ENST00000370225.3:c.454C>T

NM_000350.2:c.454C>T

Pathogenic

PM2_Supporting PVS1 PS4

BS1

Evidence Links 0

Expert Panel

ABCA4 VCEP

Criteria Specification Information

Criteria Specification: ClinGen ABCA4 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCA4 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ABCA4 VCEP

The NM_000350.3:c.454C>T (p.Arg152Ter) variant in ABCA4 is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 5/50 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). The total minor allele frequency in gnomAD v4.1.0 for this variant is 0.00001487 (24/1613738 alleles) which is lower than the ClinGen ABCA4 VCEP threshold of 0.0001 for disease in this gene (PM2_Supporting). The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls with an OR of 255.5 and the CI is 83.60 to 1308.99, which is above the ABCA4 VCEP threshold of ≥5, where the CI does not contain 1 (PS4; PMID: 35120629). In summary, this variant meets the criteria to be classified as pathogenic for ABCA4-related retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen ABCA4 VCEP (v1.0.0): PVS1, PS4, PM2_Supporting.

PM2_Supporting

The total minor allele frequency in gnomAD v4.1.0 for this variant is 0.00001487 (24/1613738 alleles) which is lower than the ClinGen ABCA4 VCEP threshold of 0.0001 for disease in this gene. (PM2_Supporting)

PVS1

The c.454C>T (p.Arg152Ter) (NM_000350.3) variant in ABCA4 is nonsense variant located in exon 5 out of 50, and introduces a premature stop codon between codons 1-2255 (PVS1).

PS4

The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls. The OR is 255.5 and the CI is 83.60 to 1308.99, which is above the ABCA4 VCEP threshold of ≥5, where the CI does not contain 1 (PS4; PMID: 35120629).

BS1

The GroupMax filtering allele frequency in gnomAD v4.1.0 is 0.00001107 (European non-Finnish alleles). which is lower than the ClinGen ABCA4 VCEP’s threshold for BS1 (>0.0163). Therefore, BS1 criterion is not met.

Curation History

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