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_014336.5(AIPL1):c.111C>T (p.Phe37=)

CA227864

99789 (ClinVar)

Gene: AIPL1 (HGNC:23746)

Condition: AIPL1-related retinopathy (MONDO:0100438)

Inheritance Mode: Autosomal recessive inheritance

UUID: 02a43879-4d81-4514-8a4a-c12b5ef8b8aa

Approved on: 2025-09-29

Published on: 2025-09-29

HGVS expressions

NM_014336.5(AIPL1):c.111C>T (p.Phe37=)

NM_014336.5:c.111C>T

NC_000017.11:g.6434084G>A

CM000679.2:g.6434084G>A

NC_000017.10:g.6337404G>A

CM000679.1:g.6337404G>A

NC_000017.9:g.6278128G>A

NG_008474.1:g.6116C>T

ENST00000381129.8:c.111C>T

ENST00000250087.9:c.111C>T

ENST00000381128.2:c.169C>T

ENST00000381129.7:c.111C>T

ENST00000570466.5:c.97-52C>T

ENST00000570584.5:c.86C>T

ENST00000571740.5:c.111C>T

ENST00000574506.5:c.97-22C>T

ENST00000574913.1:c.111C>T

ENST00000575265.5:c.111C>T

ENST00000576307.5:c.96+925C>T

ENST00000576776.5:c.111C>T

ENST00000621374.4:c.111C>T

NM_001033054.2:c.111C>T

NM_001033055.2:c.96+925C>T

NM_001285399.2:c.97-22C>T

NM_001285400.2:c.97-52C>T

NM_001285401.2:c.111C>T

NM_001285402.1:c.-7C>T

NM_001285403.2:c.111C>T

NM_014336.4:c.111C>T

NM_001033054.3:c.111C>T

NM_001033055.3:c.96+925C>T

NM_001285399.3:c.97-22C>T

NM_001285400.3:c.97-52C>T

NM_001285401.3:c.111C>T

NM_001285402.2:c.-7C>T

NM_001285403.3:c.111C>T

NM_001285403.4:c.111C>T

Benign

BS2 BP4 BP7 BA1

Evidence Links 0

Expert Panel

Leber Congenital Amaurosis/early onset Retinal Dystrophy VCEP

Criteria Specification Information

Criteria Specification: ClinGen Leber Congenital Amaurosis/early onset Retinal Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for AIPL1 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Leber Congenital Amaurosis/early onset Retinal Dystrophy VCEP

NM_014336.5(AIPL1):c.111C>T (p.Phe37=) is a synonymous variant in exon 2 of 6. The change from C to T at c.111 is not predicted to change the amino acid phenylalanine at position p.37. This variant is present in gnomAD v.4.1.0 at a Grpmax allele frequency of 0.03109, with 37005 alleles / 1,179,952 total alleles in the European (non-Finnish) population, which is higher than the ClinGen LCA/eoRD VCEP BA1 threshold of >0.0057 (BA1). Additionally, the variant has been found in the homozygous state in 748 adult individuals in gnomAD which exceeds the LCA/eoRD VCEP threshold of ≥6 (gnomAD version 4.1.0; BS2). The splicing impact predictor SpliceAI gives a delta score of 0.08, which is below the ClinGen LCA/eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4, BP7). In summary, this variant meets the criteria to be classified as Benign for AIPL1-related retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA/eoRD VCEP: BA1, BS2, BP4, and BP7. (VCEP specifications version 1.0.0; date of approval 09/24/2025).

BS2

This variant has been found in the homozygous state in 748 adult individuals in gnomAD which exceeds the LCA/eoRD VCEP threshold of ≥6 (gnomAD version 4.1.0; BS2)

BP4

The splicing impact predictor SpliceAI gives a delta score of 0.08, which is below the ClinGen LCA/eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4).

BP7

The splicing impact predictor SpliceAI gives a delta score of 0.08, which is below the ClinGen LCA/eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing and the nucleotide has a phyloP score of 2.35057 and is not predicted to be highly conserved (BP4, BP7).

BA1

This variant is present in gnomAD v.4.1.0 at a Grpmax allele frequency of 0.03109, with 37005 alleles /1179952 total alleles in the European (non-Finnish) population, which is higher than the ClinGen LCA/eoRD VCEP BA1 threshold of >0.0057 (BA1).

Curation History

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