chr7-116525092-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001753.5(CAV1):c.30G>C(p.Glu10Asp) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 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_001753.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CAV1 | NM_001753.5 | c.30G>C | p.Glu10Asp | missense_variant, splice_region_variant | Exon 1 of 3 | ENST00000341049.7 | NP_001744.2 | |
CAV1 | NM_001172895.1 | c.-777G>C | 5_prime_UTR_variant | Exon 1 of 3 | NP_001166366.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Pulmonary hypertension, primary, 3 Uncertain:1
The heterozygous c.30G>C (p.Glu10Asp) variant identified in the CAV1 gene substitutes a Glutamic Acid for Aspartic Acid at amino acid 10/179 (exon 1/3). The p.Glu10 residue is the last amino acid in exon 1, and he c.30G is the last nucleotide in exon 1, and in addition to the missense change at the protein level, this nucleotidemay also be involved in splicing. Both the Glutamic Acid at this position as well as the Guanine nucleotide at this position are well conserved. This variant is absent from gnomAD(v3.0) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms do not agree on the effect of this missense variant, as it is predicted both Neutral (Provean; score:-0.29) and Damaging (SIFT; score:0.049) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The p.Glu10 residue is within a region of CAV1 that is required for homooligomerization (UniProtKB:Q03135). Given the lack of compelling evidence for its pathogenicity, the c.30G>C (p.Glu10Asp) variant identified in the CAV1 gene is reported as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.