rs2238043

Positions:

• chr12-2166497-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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]

LOC107984131 (HGNC:):

ACMG classification

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
CACNA1C	NM_000719.7	c.477+46067G>A		intron_variant		ENST00000399655.6
CACNA1C	NM_001167623.2	c.477+46067G>A		intron_variant		ENST00000399603.6
LOC107984131	XR_001749435.2	n.17707G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1C	ENST00000399603.6	c.477+46067G>A		intron_variant		5	NM_001167623.2
CACNA1C	ENST00000399655.6	c.477+46067G>A		intron_variant		1	NM_000719.7

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72859 AN: 151870 Hom.: 17834 Cov.: 32

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

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

Other links and lift over

dbSNP: rs2238043; hg19: chr12-2275663;