rs201249348
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_002890.3(RASA1):c.1935-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000563 in 1,609,886 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 predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002890.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RASA1 | NM_002890.3 | c.1935-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000274376.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RASA1 | ENST00000274376.11 | c.1935-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_002890.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000388 AC: 59AN: 152130Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000296 AC: 74AN: 249690Hom.: 0 AF XY: 0.000281 AC XY: 38AN XY: 135360
GnomAD4 exome AF: 0.000581 AC: 847AN: 1457756Hom.: 0 Cov.: 31 AF XY: 0.000582 AC XY: 422AN XY: 725328
GnomAD4 genome ? AF: 0.000388 AC: 59AN: 152130Hom.: 0 Cov.: 31 AF XY: 0.000323 AC XY: 24AN XY: 74332
ClinVar
Submissions by phenotype
Capillary malformation-arteriovenous malformation syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | This sequence change falls in intron 14 of the RASA1 gene. It does not directly change the encoded amino acid sequence of the RASA1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs201249348, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with RASA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 464855). 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 is not likely to affect RNA splicing. 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2020 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 25, 2022 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at