chr1-94062587-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 4P and 12B. PM1PM5BP4_StrongBS1BS2
The NM_000350.3(ABCA4):c.1927G>A(p.Val643Met) variant causes a missense change. The variant allele was found at a frequency of 0.000896 in 1,614,030 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V643G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000350.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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ABCA4 | ENST00000370225.4 | c.1927G>A | p.Val643Met | missense_variant | Exon 13 of 50 | 1 | NM_000350.3 | ENSP00000359245.3 | ||
ABCA4 | ENST00000649773.1 | c.1927G>A | p.Val643Met | missense_variant | Exon 13 of 19 | ENSP00000496882.1 |
Frequencies
GnomAD3 genomes AF: 0.00463 AC: 705AN: 152126Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00132 AC: 332AN: 251106Hom.: 2 AF XY: 0.00108 AC XY: 147AN XY: 135702
GnomAD4 exome AF: 0.000506 AC: 739AN: 1461786Hom.: 8 Cov.: 37 AF XY: 0.000446 AC XY: 324AN XY: 727200
GnomAD4 genome AF: 0.00464 AC: 707AN: 152244Hom.: 6 Cov.: 32 AF XY: 0.00426 AC XY: 317AN XY: 74428
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2Other:1
ABCA4: PM3:Strong, PM2:Supporting, PP3, BS2 -
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This variant is associated with the following publications: (PMID: 22995991, 24265693, 25066811, 28044389, 25082885, 25097241, 25910913, 11527935, 22328824, 29925512, 32619608) -
Retinal dystrophy Uncertain:2
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Retinitis Pigmentosa, Recessive Benign:1
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not specified Benign:1
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Stargardt Disease, Recessive Benign:1
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Severe early-childhood-onset retinal dystrophy Benign:1
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ABCA4-related disorder Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Cone-Rod Dystrophy, Recessive Benign:1
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Macular degeneration Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at