12-2669044-G-T

Variant names:

• chr12-2669044-G-T
• rs369267978
• NM_000719.7:c.4726+9G>T

Variant summary

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

The NM_000719.7(CACNA1C):​c.4726+9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,431,186 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CACNA1C NM_000719.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60

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-AS2 (HGNC:):

CACNA1C-AS2 (HGNC:40118): (CACNA1C antisense RNA 2)

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=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1C	NM_000719.7	c.4726+9G>T		intron_variant	Intron 38 of 46	ENST00000399655.6	NP_000710.5
CACNA1C	NM_001167623.2	c.4726+9G>T		intron_variant	Intron 38 of 46	ENST00000399603.6	NP_001161095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1C	ENST00000399603.6	c.4726+9G>T		intron_variant	Intron 38 of 46	5	NM_001167623.2	ENSP00000382512.1
CACNA1C	ENST00000399655.6	c.4726+9G>T		intron_variant	Intron 38 of 46	1	NM_000719.7	ENSP00000382563.1
CACNA1C	ENST00000682544.1	c.4960+9G>T		intron_variant	Intron 40 of 49			ENSP00000507184.1
CACNA1C	ENST00000406454.8	c.4726+9G>T		intron_variant	Intron 38 of 47	5		ENSP00000385896.3
CACNA1C	ENST00000399634.6	c.4693+9G>T		intron_variant	Intron 37 of 46	5		ENSP00000382542.2
CACNA1C	ENST00000683824.1	c.4891+9G>T		intron_variant	Intron 39 of 47			ENSP00000507867.1
CACNA1C	ENST00000347598.9	c.4870+9G>T		intron_variant	Intron 40 of 48	1		ENSP00000266376.6
CACNA1C	ENST00000344100.7	c.4792+9G>T		intron_variant	Intron 38 of 46	1		ENSP00000341092.3
CACNA1C	ENST00000327702.12	c.4726+9G>T		intron_variant	Intron 38 of 47	1		ENSP00000329877.7
CACNA1C	ENST00000399617.6	c.4726+9G>T		intron_variant	Intron 38 of 47	5		ENSP00000382526.1
CACNA1C	ENST00000682462.1	c.4816+9G>T		intron_variant	Intron 38 of 46			ENSP00000507105.1
CACNA1C	ENST00000683781.1	c.4816+9G>T		intron_variant	Intron 38 of 46			ENSP00000507434.1
CACNA1C	ENST00000683840.1	c.4816+9G>T		intron_variant	Intron 38 of 46			ENSP00000507612.1
CACNA1C	ENST00000683956.1	c.4816+9G>T		intron_variant	Intron 38 of 46			ENSP00000506882.1
CACNA1C	ENST00000399638.5	c.4810+9G>T		intron_variant	Intron 39 of 47	1		ENSP00000382547.1
CACNA1C	ENST00000335762.10	c.4801+9G>T		intron_variant	Intron 39 of 47	5		ENSP00000336982.5
CACNA1C	ENST00000399606.5	c.4786+9G>T		intron_variant	Intron 39 of 47	1		ENSP00000382515.1
CACNA1C	ENST00000399621.5	c.4726+9G>T		intron_variant	Intron 38 of 46	1		ENSP00000382530.1
CACNA1C	ENST00000399637.5	c.4726+9G>T		intron_variant	Intron 38 of 46	1		ENSP00000382546.1
CACNA1C	ENST00000402845.7	c.4726+9G>T		intron_variant	Intron 38 of 46	1		ENSP00000385724.3
CACNA1C	ENST00000399629.5	c.4777+9G>T		intron_variant	Intron 38 of 46	1		ENSP00000382537.1
CACNA1C	ENST00000682336.1	c.4768+9G>T		intron_variant	Intron 38 of 46			ENSP00000507898.1
CACNA1C	ENST00000399591.5	c.4693+9G>T		intron_variant	Intron 37 of 45	1		ENSP00000382500.1
CACNA1C	ENST00000399595.5	c.4693+9G>T		intron_variant	Intron 37 of 45	1		ENSP00000382504.1
CACNA1C	ENST00000399649.5	c.4687+9G>T		intron_variant	Intron 37 of 45	1		ENSP00000382557.1
CACNA1C	ENST00000399597.5	c.4726+9G>T		intron_variant	Intron 38 of 46	1		ENSP00000382506.1
CACNA1C	ENST00000399601.5	c.4726+9G>T		intron_variant	Intron 38 of 46	1		ENSP00000382510.1
CACNA1C	ENST00000399641.6	c.4726+9G>T		intron_variant	Intron 38 of 46	1		ENSP00000382549.1
CACNA1C	ENST00000399644.5	c.4726+9G>T		intron_variant	Intron 38 of 46	1		ENSP00000382552.1
CACNA1C	ENST00000682835.1	c.4726+9G>T		intron_variant	Intron 38 of 46			ENSP00000507282.1
CACNA1C	ENST00000683482.1	c.4717+9G>T		intron_variant	Intron 38 of 46			ENSP00000507169.1
CACNA1C	ENST00000682686.1	c.4693+9G>T		intron_variant	Intron 37 of 45			ENSP00000507309.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000801 AC: 2 AN: 249784 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135500

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1431186 Hom.: 0 Cov.: 25 AF XY: 0.00000140 AC XY: 1 AN XY: 713984

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000337

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0020
DANN	Benign	0.85

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: rs369267978; hg19: chr12-2778210;