rs367763190

Variant names:

• chr12-2120316-C-A
• NM_000719.7:c.372-9C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-2120316-C-A
• chr12-2120316-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000719.7(CACNA1C):​c.372-9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,255,226 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: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: CACNA1C NM_000719.7 intron
• Scores: Splicing: ADA: 0.007103
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.868

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1C	NM_000719.7	c.372-9C>A		intron_variant	Intron 2 of 46	ENST00000399655.6	NP_000710.5
CACNA1C	NM_001167623.2	c.372-9C>A		intron_variant	Intron 2 of 46	ENST00000399603.6	NP_001161095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1C	ENST00000399603.6	c.372-9C>A		intron_variant	Intron 2 of 46	5	NM_001167623.2	ENSP00000382512.1
CACNA1C	ENST00000399655.6	c.372-9C>A		intron_variant	Intron 2 of 46	1	NM_000719.7	ENSP00000382563.1
CACNA1C	ENST00000682544.1	c.462-9C>A		intron_variant	Intron 2 of 49			ENSP00000507184.1
CACNA1C	ENST00000406454.8	c.372-9C>A		intron_variant	Intron 2 of 47	5		ENSP00000385896.3
CACNA1C	ENST00000399634.6	c.372-9C>A		intron_variant	Intron 2 of 46	5		ENSP00000382542.2
CACNA1C	ENST00000683824.1	c.462-9C>A		intron_variant	Intron 2 of 47			ENSP00000507867.1
CACNA1C	ENST00000347598.9	c.372-9C>A		intron_variant	Intron 2 of 48	1		ENSP00000266376.6
CACNA1C	ENST00000344100.7	c.372-9C>A		intron_variant	Intron 2 of 46	1		ENSP00000341092.3
CACNA1C	ENST00000327702.12	c.372-9C>A		intron_variant	Intron 2 of 47	1		ENSP00000329877.7
CACNA1C	ENST00000399617.6	c.372-9C>A		intron_variant	Intron 2 of 47	5		ENSP00000382526.1
CACNA1C	ENST00000682462.1	c.462-9C>A		intron_variant	Intron 2 of 46			ENSP00000507105.1
CACNA1C	ENST00000683781.1	c.462-9C>A		intron_variant	Intron 2 of 46			ENSP00000507434.1
CACNA1C	ENST00000683840.1	c.462-9C>A		intron_variant	Intron 2 of 46			ENSP00000507612.1
CACNA1C	ENST00000683956.1	c.462-9C>A		intron_variant	Intron 2 of 46			ENSP00000506882.1
CACNA1C	ENST00000399638.5	c.372-9C>A		intron_variant	Intron 2 of 47	1		ENSP00000382547.1
CACNA1C	ENST00000335762.10	c.372-9C>A		intron_variant	Intron 2 of 47	5		ENSP00000336982.5
CACNA1C	ENST00000399606.5	c.372-9C>A		intron_variant	Intron 2 of 47	1		ENSP00000382515.1
CACNA1C	ENST00000399621.5	c.372-9C>A		intron_variant	Intron 2 of 46	1		ENSP00000382530.1
CACNA1C	ENST00000399637.5	c.372-9C>A		intron_variant	Intron 2 of 46	1		ENSP00000382546.1
CACNA1C	ENST00000402845.7	c.372-9C>A		intron_variant	Intron 2 of 46	1		ENSP00000385724.3
CACNA1C	ENST00000399629.5	c.372-9C>A		intron_variant	Intron 2 of 46	1		ENSP00000382537.1
CACNA1C	ENST00000682336.1	c.372-9C>A		intron_variant	Intron 2 of 46			ENSP00000507898.1
CACNA1C	ENST00000399591.5	c.372-9C>A		intron_variant	Intron 2 of 45	1		ENSP00000382500.1
CACNA1C	ENST00000399595.5	c.372-9C>A		intron_variant	Intron 2 of 45	1		ENSP00000382504.1
CACNA1C	ENST00000399649.5	c.372-9C>A		intron_variant	Intron 2 of 45	1		ENSP00000382557.1
CACNA1C	ENST00000399597.5	c.372-9C>A		intron_variant	Intron 2 of 46	1		ENSP00000382506.1
CACNA1C	ENST00000399601.5	c.372-9C>A		intron_variant	Intron 2 of 46	1		ENSP00000382510.1
CACNA1C	ENST00000399641.6	c.372-9C>A		intron_variant	Intron 2 of 46	1		ENSP00000382549.1
CACNA1C	ENST00000399644.5	c.372-9C>A		intron_variant	Intron 2 of 46	1		ENSP00000382552.1
CACNA1C	ENST00000682835.1	c.372-9C>A		intron_variant	Intron 2 of 46			ENSP00000507282.1
CACNA1C	ENST00000683482.1	c.372-9C>A		intron_variant	Intron 2 of 46			ENSP00000507169.1
CACNA1C	ENST00000682686.1	c.372-9C>A		intron_variant	Intron 2 of 45			ENSP00000507309.1
CACNA1C	ENST00000682152.1	c.321-9C>A		intron_variant	Intron 1 of 5			ENSP00000506759.1
CACNA1C	ENST00000480911.6	n.372-9C>A		intron_variant	Intron 2 of 26	5		ENSP00000437936.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000159 AC: 2 AN: 1255226 Hom.: 0 Cov.: 19 AF XY: 0.00000157 AC XY: 1 AN XY: 636026

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: 0.0000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0071
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-2229482;