rs11062241

Positions:

• chr12-2477420-C-T

Variant summary

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

The NM_000719.7(CACNA1C):​c.758-8684C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 152,216 control chromosomes in the GnomAD database, including 1,066 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 0.082 (1066 hom., cov: 32)
• Consequence: CACNA1C NM_000719.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1C	NM_000719.7	c.758-8684C>T		intron_variant		ENST00000399655.6	NP_000710.5
CACNA1C	NM_001167623.2	c.758-8684C>T		intron_variant		ENST00000399603.6	NP_001161095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1C	ENST00000399603.6	c.758-8684C>T		intron_variant		5	NM_001167623.2	ENSP00000382512
CACNA1C	ENST00000399655.6	c.758-8684C>T		intron_variant		1	NM_000719.7	ENSP00000382563

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12473 AN: 152098 Hom.: 1063 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0442

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.0359

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0296

Gnomad OTH AF: 0.0665

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0821 AC: 12497 AN: 152216 Hom.: 1066 Cov.: 32 AF XY: 0.0804 AC XY: 5982 AN XY: 74430

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.0441

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.0361

Gnomad4 SAS AF: 0.0253

Gnomad4 FIN AF: 0.0107

Gnomad4 NFE AF: 0.0296

Gnomad4 OTH AF: 0.0658

Alfa AF: 0.0514 Hom.: 192

Bravo AF: 0.0923

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.23
DANN	Benign	0.77

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: rs11062241; hg19: chr12-2586586;