rs150838215
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS1
The NM_001128840.3(CACNA1D):c.6437G>A(p.Arg2146Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000251 in 1,594,098 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001128840.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1D | NM_000720.4 | c.6497G>A | p.Arg2166Lys | missense_variant | Exon 49 of 49 | ENST00000288139.11 | NP_000711.1 | |
CACNA1D | NM_001128840.3 | c.6437G>A | p.Arg2146Lys | missense_variant | Exon 48 of 48 | ENST00000350061.11 | NP_001122312.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1D | ENST00000288139.11 | c.6497G>A | p.Arg2166Lys | missense_variant | Exon 49 of 49 | 1 | NM_000720.4 | ENSP00000288139.3 | ||
CACNA1D | ENST00000350061.11 | c.6437G>A | p.Arg2146Lys | missense_variant | Exon 48 of 48 | 1 | NM_001128840.3 | ENSP00000288133.5 |
Frequencies
GnomAD3 genomes AF: 0.00129 AC: 197AN: 152196Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000382 AC: 92AN: 240542Hom.: 1 AF XY: 0.000277 AC XY: 36AN XY: 129854
GnomAD4 exome AF: 0.000141 AC: 203AN: 1441784Hom.: 0 Cov.: 31 AF XY: 0.000109 AC XY: 78AN XY: 714094
GnomAD4 genome AF: 0.00129 AC: 197AN: 152314Hom.: 1 Cov.: 32 AF XY: 0.00118 AC XY: 88AN XY: 74474
ClinVar
Submissions by phenotype
not specified Benign:2
Arg2166Lys in exon 49 of CACNA1D: This variant is not expected to have clinical significance because it has been identified in 0.5% (22/4406) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs150838215). -
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not provided Benign:2
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Inborn genetic diseases Benign:1
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. -
CACNA1D-related disorder Benign:1
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). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at