rs61754022
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000350.3(ABCA4):c.1761-50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,585,642 control chromosomes in the GnomAD database, including 255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 12 hom., cov: 32)
Exomes 𝑓: 0.017 ( 243 hom. )
Consequence
ABCA4
NM_000350.3 intron
NM_000350.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0770
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 1-94062803-C-T is Benign according to our data. Variant chr1-94062803-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 99078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0121 (1848/152240) while in subpopulation NFE AF= 0.0194 (1320/68014). AF 95% confidence interval is 0.0185. There are 12 homozygotes in gnomad4. There are 879 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 12 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCA4 | NM_000350.3 | c.1761-50G>A | intron_variant | ENST00000370225.4 | |||
ABCA4 | XM_047416704.1 | c.1761-50G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCA4 | ENST00000370225.4 | c.1761-50G>A | intron_variant | 1 | NM_000350.3 | P1 | |||
ABCA4 | ENST00000649773.1 | c.1761-50G>A | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0121 AC: 1847AN: 152122Hom.: 12 Cov.: 32
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GnomAD3 exomes AF: 0.0141 AC: 3236AN: 228846Hom.: 21 AF XY: 0.0144 AC XY: 1771AN XY: 123364
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GnomAD4 exome AF: 0.0168 AC: 24061AN: 1433402Hom.: 243 Cov.: 28 AF XY: 0.0168 AC XY: 11999AN XY: 712904
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GnomAD4 genome ? AF: 0.0121 AC: 1848AN: 152240Hom.: 12 Cov.: 32 AF XY: 0.0118 AC XY: 879AN XY: 74432
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1Other:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
not provided, no classification provided | literature only | Retina International | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
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