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.6285T>C (p.Asp2095=)

CA285825

99444 (ClinVar)

Gene: ABCA4 (HGNC:24)

Condition: ABCA4-related retinopathy (MONDO:0800406)

Inheritance Mode: Autosomal recessive inheritance

UUID: ab6237c1-841a-4f44-a1ab-2dcf9c825788

Approved on: 2026-05-26

Published on: 2026-05-26

HGVS expressions

NM_000350.3(ABCA4):c.6285T>C (p.Asp2095=)

NM_000350.3:c.6285T>C

NC_000001.11:g.94001103A>G

CM000663.2:g.94001103A>G

NC_000001.10:g.94466659A>G

CM000663.1:g.94466659A>G

NC_000001.9:g.94239247A>G

NG_009073.1:g.125047T>C

ENST00000370225.4:c.6285T>C

ENST00000370225.3:c.6285T>C

ENST00000536513.5:c.2661T>C

NM_000350.2:c.6285T>C

Benign

BP7 BA1

PM3 PS4 BP4

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(ABCA4):c.6285T>C variant is a synonymous variant, p.Asp2095=. The GroupMax filtering allele frequency in gnomAD v4.1.0 is 0.6547, which is greater than the ClinGen ABCA4 VCEP’s threshold for BA1 (>0.163). The computational splicing predictor SpliceAI gives this synonymous variant a delta score of 0.03 for donor gain, which is below the ClinGen ABCA4 VCEP BP7 threshold of <0.1 and does not strongly predict a splicing defect (BP7_Moderate). In summary, this variant meets the criteria to be classified as benign for ABCA4-related retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen ABCA4 VCEP (Specification Version 1.0.0): BA1, BP7_Moderate.

BP7

The computational splicing predictor SpliceAI gives this synonymous (silent) variant a delta score of 0.03 for donor gain which is below the ClinGen ABCA4 VCEP BP7 threshold of <0.1 and does not strongly predict a splicing defect. To our knowledge, there is no known conflicting minigene or other functional data available (BP7_Moderate).

BA1

The GroupMax filtering allele frequency in gnomAD v4.1.0 is 0.6547, which is greater than the ClinGen ABCA4 VCEP’s threshold for BA1 (>0.163), and therefore meets this criterion (BA1).

PM3

This variant has been detected in at least 94 individuals with ABCA4-related retinopathy. Of those individuals, 2 were compound heterozygous for the variant and a pathogenic variant (c.6445C>T p.(R2149X); c.5882G>A p.(Gly1961Glu)) and neither of those were confirmed in trans (PM3= 1 point; PMIDs: 20801516, 28002570, 28118664). However, since this variant meets BA1, PM3 is not applicable.

PS4

The prevalence of the variant in affected individuals is not significantly increased compared with the prevalence in controls. The OR is 0 and the CI is 0-0 (PMID: 35120629).

BP4

The computational predictor CADD gives a score of 0.305 which is less than or equal to the threshold of ≤17.3, evidence that does not predict a damaging effect on ABCA4 function (BP4_Moderate). This code will not be applied since BP7 is being applied at the moderate weight instead.

Curation History

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