rs750666820
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_021098.3(CACNA1H):c.6260G>A(p.Gly2087Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000909 in 1,539,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_021098.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1H | NM_021098.3 | c.6260G>A | p.Gly2087Asp | missense_variant | 35/35 | ENST00000348261.11 | NP_066921.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1H | ENST00000348261.11 | c.6260G>A | p.Gly2087Asp | missense_variant | 35/35 | 1 | NM_021098.3 | ENSP00000334198.7 | ||
CACNA1H | ENST00000565831.6 | c.6242G>A | p.Gly2081Asp | missense_variant | 33/33 | 1 | ENSP00000455840.1 | |||
CACNA1H | ENST00000638323.1 | c.6221G>A | p.Gly2074Asp | missense_variant | 35/35 | 5 | ENSP00000492267.1 | |||
CACNA1H | ENST00000569107.5 | c.2498G>A | p.Gly833Asp | missense_variant | 17/17 | 1 | ENSP00000454990.2 | |||
CACNA1H | ENST00000564231.5 | c.2450G>A | p.Gly817Asp | missense_variant | 18/18 | 1 | ENSP00000457555.2 | |||
CACNA1H | ENST00000562079.5 | c.2432G>A | p.Gly811Asp | missense_variant | 17/17 | 1 | ENSP00000454581.2 | |||
CACNA1H | ENST00000639478.1 | n.*1308G>A | non_coding_transcript_exon_variant | 35/35 | 5 | ENSP00000491945.1 | ||||
CACNA1H | ENST00000640028.1 | n.*4078G>A | non_coding_transcript_exon_variant | 35/35 | 5 | ENSP00000491488.1 | ||||
CACNA1H | ENST00000639478.1 | n.*1308G>A | 3_prime_UTR_variant | 35/35 | 5 | ENSP00000491945.1 | ||||
CACNA1H | ENST00000640028.1 | n.*4078G>A | 3_prime_UTR_variant | 35/35 | 5 | ENSP00000491488.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 35
GnomAD4 exome AF: 0.00000937 AC: 13AN: 1387618Hom.: 0 Cov.: 72 AF XY: 0.00000583 AC XY: 4AN XY: 686132
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 74324
ClinVar
Submissions by phenotype
Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 03, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2087 of the CACNA1H protein (p.Gly2087Asp). This variant is not present in population databases (gnomAD no frequency). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CACNA1H protein function. This variant has not been reported in the literature in individuals affected with CACNA1H-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at