rs746541266
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000350.3(ABCA4):c.3871C>T(p.Gln1291Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000350.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCA4 | NM_000350.3 | c.3871C>T | p.Gln1291Ter | stop_gained | 27/50 | ENST00000370225.4 | |
ABCA4 | XM_047416704.1 | c.3649C>T | p.Gln1217Ter | stop_gained | 26/49 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCA4 | ENST00000370225.4 | c.3871C>T | p.Gln1291Ter | stop_gained | 27/50 | 1 | NM_000350.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000407 AC: 1AN: 245650Hom.: 0 AF XY: 0.00000750 AC XY: 1AN XY: 133376
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459104Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 725896
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2018 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 06, 2020 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ABCA4 are known to be pathogenic (PMID: 10958761, 24938718, 25312043, 26780318). This variant has been observed in individual(s) with ABCA4-related conditions (PMID: 25474345, 28118664, 29555955). ClinVar contains an entry for this variant (Variation ID: 236106). This variant is present in population databases (rs746541266, ExAC 0.002%). This sequence change creates a premature translational stop signal (p.Gln1291*) in the ABCA4 gene. It is expected to result in an absent or disrupted protein product. - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 31, 2019 | - - |
Age related macular degeneration 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Dec 05, 2019 | This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PM3,PP5. - |
Severe early-childhood-onset retinal dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg | Jan 01, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at