rs4847281
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000350.3(ABCA4):āc.141A>Gā(p.Pro47=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 1,613,766 control chromosomes in the GnomAD database, including 803,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.99 ( 74421 hom., cov: 31)
Exomes š: 1.0 ( 729056 hom. )
Consequence
ABCA4
NM_000350.3 synonymous
NM_000350.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.25
Genes affected
ABCA4 (HGNC:34): (ATP binding cassette subfamily A member 4) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This protein is a retina-specific ABC transporter with N-retinylidene-PE as a substrate. It is expressed exclusively in retina photoreceptor cells, and the gene product mediates transport of an essental molecule, all-trans-retinal aldehyde (atRAL), across the photoreceptor cell membrane. Mutations in this gene are found in patients diagnosed with Stargardt disease, a form of juvenile-onset macular degeneration. Mutations in this gene are also associated with retinitis pigmentosa-19, cone-rod dystrophy type 3, early-onset severe retinal dystrophy, fundus flavimaculatus, and macular degeneration age-related 2. [provided by RefSeq, Sep 2019]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
Variant 1-94112992-T-C is Benign according to our data. Variant chr1-94112992-T-C is described in ClinVar as [Benign]. Clinvar id is 166618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.26 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCA4 | NM_000350.3 | c.141A>G | p.Pro47= | synonymous_variant | 2/50 | ENST00000370225.4 | |
ABCA4 | XM_047416704.1 | c.141A>G | p.Pro47= | synonymous_variant | 2/49 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCA4 | ENST00000370225.4 | c.141A>G | p.Pro47= | synonymous_variant | 2/50 | 1 | NM_000350.3 | P1 | |
ABCA4 | ENST00000649773.1 | c.141A>G | p.Pro47= | synonymous_variant | 2/19 |
Frequencies
GnomAD3 genomes ? AF: 0.989 AC: 150416AN: 152160Hom.: 74372 Cov.: 31
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GnomAD3 exomes AF: 0.997 AC: 250709AN: 251442Hom.: 124997 AF XY: 0.998 AC XY: 135595AN XY: 135890
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GnomAD4 exome AF: 0.999 AC: 1459772AN: 1461488Hom.: 729056 Cov.: 42 AF XY: 0.999 AC XY: 726343AN XY: 727068
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GnomAD4 genome ? AF: 0.988 AC: 150524AN: 152278Hom.: 74421 Cov.: 31 AF XY: 0.988 AC XY: 73599AN XY: 74460
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 17, 2013 | - - |
Age related macular degeneration 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Severe early-childhood-onset retinal dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Retinitis pigmentosa 19 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Cone-rod dystrophy 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at