rs2238043

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000719.7(CACNA1C):​c.477+46067G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,988 control chromosomes in the GnomAD database, including 17,865 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 17865 hom., cov: 32)

Consequence

CACNA1C
NM_000719.7 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.132
Variant links:
Genes affected
CACNA1C (HGNC:1390): (calcium voltage-gated channel subunit alpha1 C) This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits. [provided by RefSeq, Oct 2012]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CACNA1CNM_000719.7 linkuse as main transcriptc.477+46067G>A intron_variant ENST00000399655.6
CACNA1CNM_001167623.2 linkuse as main transcriptc.477+46067G>A intron_variant ENST00000399603.6
LOC107984131XR_001749435.2 linkuse as main transcriptn.17707G>A non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CACNA1CENST00000399603.6 linkuse as main transcriptc.477+46067G>A intron_variant 5 NM_001167623.2 Q13936-37
CACNA1CENST00000399655.6 linkuse as main transcriptc.477+46067G>A intron_variant 1 NM_000719.7 Q13936-12

Frequencies

GnomAD3 genomes
AF:
0.480
AC:
72859
AN:
151870
Hom.:
17834
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.555
Gnomad AMI
AF:
0.470
Gnomad AMR
AF:
0.443
Gnomad ASJ
AF:
0.377
Gnomad EAS
AF:
0.576
Gnomad SAS
AF:
0.593
Gnomad FIN
AF:
0.479
Gnomad MID
AF:
0.386
Gnomad NFE
AF:
0.434
Gnomad OTH
AF:
0.442
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.480
AC:
72950
AN:
151988
Hom.:
17865
Cov.:
32
AF XY:
0.484
AC XY:
35960
AN XY:
74276
show subpopulations
Gnomad4 AFR
AF:
0.555
Gnomad4 AMR
AF:
0.443
Gnomad4 ASJ
AF:
0.377
Gnomad4 EAS
AF:
0.576
Gnomad4 SAS
AF:
0.593
Gnomad4 FIN
AF:
0.479
Gnomad4 NFE
AF:
0.434
Gnomad4 OTH
AF:
0.448
Alfa
AF:
0.457
Hom.:
8719
Bravo
AF:
0.475
Asia WGS
AF:
0.583
AC:
2023
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
4.7
DANN
Benign
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2238043; hg19: chr12-2275663; API