rs147702970
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_021098.3(CACNA1H):c.1939G>A(p.Gly647Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000588 in 1,546,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G647D) has been classified as Benign.
Frequency
Consequence
NM_021098.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1H | NM_021098.3 | c.1939G>A | p.Gly647Ser | missense_variant | 9/35 | ENST00000348261.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.1939G>A | p.Gly647Ser | missense_variant | 9/35 | 1 | NM_021098.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000525 AC: 8AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000830 AC: 12AN: 144632Hom.: 0 AF XY: 0.000102 AC XY: 8AN XY: 78092
GnomAD4 exome AF: 0.0000595 AC: 83AN: 1394510Hom.: 0 Cov.: 39 AF XY: 0.0000698 AC XY: 48AN XY: 687678
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74374
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 30, 2016 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2023 | 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. - |
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at