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GeneBe

rs1006737

Variant summary

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

The NM_000719.7(CACNA1C):c.477+115699G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,038 control chromosomes in the GnomAD database, including 10,258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain risk allele (no stars).

Frequency

Genomes: 𝑓 0.35 ( 10258 hom., cov: 32)

Consequence

CACNA1C
NM_000719.7 intron

Scores

2

Clinical Significance

Uncertain risk allele no assertion criteria provided O:1

Conservation

PhyloP100: 0.248
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=-0.87).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CACNA1CNM_000719.7 linkuse as main transcriptc.477+115699G>A intron_variant ENST00000399655.6
CACNA1CNM_001167623.2 linkuse as main transcriptc.477+115699G>A intron_variant ENST00000399603.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CACNA1CENST00000399603.6 linkuse as main transcriptc.477+115699G>A intron_variant 5 NM_001167623.2 Q13936-37
CACNA1CENST00000399655.6 linkuse as main transcriptc.477+115699G>A intron_variant 1 NM_000719.7 Q13936-12

Frequencies

GnomAD3 genomes
AF:
0.354
AC:
53833
AN:
151920
Hom.:
10263
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.479
Gnomad AMI
AF:
0.315
Gnomad AMR
AF:
0.286
Gnomad ASJ
AF:
0.296
Gnomad EAS
AF:
0.0516
Gnomad SAS
AF:
0.247
Gnomad FIN
AF:
0.318
Gnomad MID
AF:
0.231
Gnomad NFE
AF:
0.335
Gnomad OTH
AF:
0.328
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.354
AC:
53869
AN:
152038
Hom.:
10258
Cov.:
32
AF XY:
0.349
AC XY:
25918
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.479
Gnomad4 AMR
AF:
0.286
Gnomad4 ASJ
AF:
0.296
Gnomad4 EAS
AF:
0.0514
Gnomad4 SAS
AF:
0.247
Gnomad4 FIN
AF:
0.318
Gnomad4 NFE
AF:
0.335
Gnomad4 OTH
AF:
0.323
Alfa
AF:
0.320
Hom.:
11497
Bravo
AF:
0.353
Asia WGS
AF:
0.150
AC:
527
AN:
3478

ClinVar

Significance: Uncertain risk allele
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Post-traumatic stress disorder Other:1
Uncertain risk allele, no assertion criteria providedresearchDepartment of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and Psychiatry-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
Cadd
Benign
5.1
Dann
Benign
0.63

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: rs1006737; hg19: chr12-2345295; API