rs774271963
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005506.4(SCARB2):c.704+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000879 in 1,592,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_005506.4 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCARB2 | NM_005506.4 | c.704+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000264896.8 | |||
SCARB2 | NM_001204255.2 | c.276-522G>A | intron_variant | ||||
SCARB2 | XM_047416429.1 | c.230+5G>A | splice_donor_5th_base_variant, intron_variant | ||||
SCARB2 | XM_047416430.1 | c.230+5G>A | splice_donor_5th_base_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCARB2 | ENST00000264896.8 | c.704+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | NM_005506.4 | P4 | |||
ENST00000651366.1 | n.103-23534C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 250092Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135230
GnomAD4 exome AF: 0.00000903 AC: 13AN: 1440130Hom.: 0 Cov.: 27 AF XY: 0.0000125 AC XY: 9AN XY: 717816
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74326
ClinVar
Submissions by phenotype
Action myoclonus-renal failure syndrome Uncertain:1Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 30, 2021 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2020 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 23515316) - |
Progressive myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 01, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 268141). This variant has been observed in individual(s) with action myoclonus-renal failure syndrome (PMID: 23515316). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs774271963, gnomAD 0.002%). This sequence change falls in intron 5 of the SCARB2 gene. It does not directly change the encoded amino acid sequence of the SCARB2 protein. It affects a nucleotide within the consensus splice site. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at