rs199594582
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS1
The NM_000388.4(CASR):c.2901C>A(p.Ile967=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,614,186 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. I967I) has been classified as Likely benign.
Frequency
Consequence
NM_000388.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CASR | NM_000388.4 | c.2901C>A | p.Ile967= | synonymous_variant | 7/7 | ENST00000639785.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CASR | ENST00000639785.2 | c.2901C>A | p.Ile967= | synonymous_variant | 7/7 | 1 | NM_000388.4 | P1 | |
CASR | ENST00000498619.4 | c.2931C>A | p.Ile977= | synonymous_variant | 7/7 | 1 | |||
CASR | ENST00000638421.1 | c.2901C>A | p.Ile967= | synonymous_variant | 7/7 | 5 | P1 | ||
CASR | ENST00000490131.7 | c.2670C>A | p.Ile890= | synonymous_variant | 5/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000259 AC: 65AN: 251436Hom.: 1 AF XY: 0.000331 AC XY: 45AN XY: 135918
GnomAD4 exome AF: 0.000146 AC: 214AN: 1461886Hom.: 4 Cov.: 71 AF XY: 0.000197 AC XY: 143AN XY: 727244
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152300Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74478
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 05, 2015 | - - |
Nephrolithiasis/nephrocalcinosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 11, 2019 | This alteration is classified as likely 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. - |
CASR-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 20, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Autosomal dominant hypocalcemia 1;C1809471:Familial hypocalciuric hypercalcemia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at