rs140482171
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PM1PM5BP4_StrongBS2
The NM_000350.3(ABCA4):c.1532G>A(p.Arg511His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000801 in 1,613,274 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. R511C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000350.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCA4 | NM_000350.3 | c.1532G>A | p.Arg511His | missense_variant | 11/50 | ENST00000370225.4 | |
LOC124904222 | XR_007066231.1 | n.203-6017C>T | intron_variant, non_coding_transcript_variant | ||||
ABCA4 | XM_047416704.1 | c.1532G>A | p.Arg511His | missense_variant | 11/49 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCA4 | ENST00000370225.4 | c.1532G>A | p.Arg511His | missense_variant | 11/50 | 1 | NM_000350.3 | P1 | |
ABCA4 | ENST00000649773.1 | c.1532G>A | p.Arg511His | missense_variant | 11/19 |
Frequencies
GnomAD3 genomes ? AF: 0.000473 AC: 72AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000778 AC: 195AN: 250676Hom.: 1 AF XY: 0.00102 AC XY: 138AN XY: 135440
GnomAD4 exome AF: 0.000836 AC: 1221AN: 1461042Hom.: 8 Cov.: 31 AF XY: 0.000973 AC XY: 707AN XY: 726682
GnomAD4 genome ? AF: 0.000473 AC: 72AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.000591 AC XY: 44AN XY: 74428
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 07, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | ABCA4: PM5, BP4 - |
Retinal dystrophy Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Blueprint Genetics | Jul 05, 2019 | - - |
Uncertain significance, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
ABCA4-related disorder Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 30, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Severe early-childhood-onset retinal dystrophy Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
Retinitis Pigmentosa, Recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Stargardt Disease, Recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Cone-Rod Dystrophy, Recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Macular degeneration Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Stargardt disease Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | Variant interpretted as Uncertain significance and reported on 12/28/2017 by GTR ID 239772. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at