rs725779

Positions:

• chr12-2019816-G-A
• chr12-2019816-G-C
• chr12-2019816-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000682544.1(CACNA1C):​c.139+48615G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: CACNA1C ENST00000682544.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442

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]

CACNA1C-IT1 (HGNC:41312): (CACNA1C intronic transcript 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1C	XM_017019926.3	c.140-15696G>A		intron_variant			XP_016875415.1
CACNA1C	XM_017019927.3	c.140-15696G>A		intron_variant			XP_016875416.1
CACNA1C	XM_047429513.1	c.140-15696G>A		intron_variant			XP_047285469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1C	ENST00000682544.1	c.139+48615G>A		intron_variant				ENSP00000507184.1
CACNA1C	ENST00000683824.1	c.139+48615G>A		intron_variant				ENSP00000507867.1
CACNA1C	ENST00000682462.1	c.139+48615G>A		intron_variant				ENSP00000507105.1
CACNA1C	ENST00000683781.1	c.139+48615G>A		intron_variant				ENSP00000507434.1
CACNA1C	ENST00000683840.1	c.139+48615G>A		intron_variant				ENSP00000507612.1
CACNA1C	ENST00000683956.1	c.139+48615G>A		intron_variant				ENSP00000506882.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs725779; hg19: chr12-2128982;