chr12-2691058-C-T

Variant names:

• chr12-2691058-C-T
• NM_000719.7:c.6276C>T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_000719.7(CACNA1C):​c.6276C>T​(p.Gly2092Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,208 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: 6.9e-7 (0 hom.)
• Consequence: CACNA1C NM_000719.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

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-AS1 (HGNC:):

CACNA1C-AS1 (HGNC:40119): (CACNA1C antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP7: Synonymous conserved (PhyloP=2.08 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1C	NM_000719.7	c.6276C>T	p.Gly2092Gly	synonymous_variant	Exon 47 of 47	ENST00000399655.6	NP_000710.5
CACNA1C	NM_001167623.2	c.6276C>T	p.Gly2092Gly	synonymous_variant	Exon 47 of 47	ENST00000399603.6	NP_001161095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1C	ENST00000399603.6	c.6276C>T	p.Gly2092Gly	synonymous_variant	Exon 47 of 47	5	NM_001167623.2	ENSP00000382512.1
CACNA1C	ENST00000399655.6	c.6276C>T	p.Gly2092Gly	synonymous_variant	Exon 47 of 47	1	NM_000719.7	ENSP00000382563.1
CACNA1C	ENST00000682544.1	c.6615C>T	p.Gly2205Gly	synonymous_variant	Exon 50 of 50			ENSP00000507184.1
CACNA1C	ENST00000406454.8	c.6489C>T	p.Gly2163Gly	synonymous_variant	Exon 48 of 48	5		ENSP00000385896.3
CACNA1C	ENST00000399634.6	c.6456C>T	p.Gly2152Gly	synonymous_variant	Exon 47 of 47	5		ENSP00000382542.2
CACNA1C	ENST00000683824.1	c.6441C>T	p.Gly2147Gly	synonymous_variant	Exon 48 of 48			ENSP00000507867.1
CACNA1C	ENST00000347598.9	c.6420C>T	p.Gly2140Gly	synonymous_variant	Exon 49 of 49	1		ENSP00000266376.6
CACNA1C	ENST00000344100.7	c.6399C>T	p.Gly2133Gly	synonymous_variant	Exon 47 of 47	1		ENSP00000341092.3
CACNA1C	ENST00000327702.12	c.6381C>T	p.Gly2127Gly	synonymous_variant	Exon 48 of 48	1		ENSP00000329877.7
CACNA1C	ENST00000399617.6	c.6381C>T	p.Gly2127Gly	synonymous_variant	Exon 48 of 48	5		ENSP00000382526.1
CACNA1C	ENST00000682462.1	c.6366C>T	p.Gly2122Gly	synonymous_variant	Exon 47 of 47			ENSP00000507105.1
CACNA1C	ENST00000683781.1	c.6366C>T	p.Gly2122Gly	synonymous_variant	Exon 47 of 47			ENSP00000507434.1
CACNA1C	ENST00000683840.1	c.6366C>T	p.Gly2122Gly	synonymous_variant	Exon 47 of 47			ENSP00000507612.1
CACNA1C	ENST00000683956.1	c.6366C>T	p.Gly2122Gly	synonymous_variant	Exon 47 of 47			ENSP00000506882.1
CACNA1C	ENST00000399638.5	c.6360C>T	p.Gly2120Gly	synonymous_variant	Exon 48 of 48	1		ENSP00000382547.1
CACNA1C	ENST00000335762.10	c.6351C>T	p.Gly2117Gly	synonymous_variant	Exon 48 of 48	5		ENSP00000336982.5
CACNA1C	ENST00000399606.5	c.6336C>T	p.Gly2112Gly	synonymous_variant	Exon 48 of 48	1		ENSP00000382515.1
CACNA1C	ENST00000399621.5	c.6333C>T	p.Gly2111Gly	synonymous_variant	Exon 47 of 47	1		ENSP00000382530.1
CACNA1C	ENST00000399637.5	c.6333C>T	p.Gly2111Gly	synonymous_variant	Exon 47 of 47	1		ENSP00000382546.1
CACNA1C	ENST00000402845.7	c.6333C>T	p.Gly2111Gly	synonymous_variant	Exon 47 of 47	1		ENSP00000385724.3
CACNA1C	ENST00000399629.5	c.6327C>T	p.Gly2109Gly	synonymous_variant	Exon 47 of 47	1		ENSP00000382537.1
CACNA1C	ENST00000682336.1	c.6318C>T	p.Gly2106Gly	synonymous_variant	Exon 47 of 47			ENSP00000507898.1
CACNA1C	ENST00000399591.5	c.6300C>T	p.Gly2100Gly	synonymous_variant	Exon 46 of 46	1		ENSP00000382500.1
CACNA1C	ENST00000399595.5	c.6300C>T	p.Gly2100Gly	synonymous_variant	Exon 46 of 46	1		ENSP00000382504.1
CACNA1C	ENST00000399649.5	c.6294C>T	p.Gly2098Gly	synonymous_variant	Exon 46 of 46	1		ENSP00000382557.1
CACNA1C	ENST00000399597.5	c.6276C>T	p.Gly2092Gly	synonymous_variant	Exon 47 of 47	1		ENSP00000382506.1
CACNA1C	ENST00000399601.5	c.6276C>T	p.Gly2092Gly	synonymous_variant	Exon 47 of 47	1		ENSP00000382510.1
CACNA1C	ENST00000399641.6	c.6276C>T	p.Gly2092Gly	synonymous_variant	Exon 47 of 47	1		ENSP00000382549.1
CACNA1C	ENST00000399644.5	c.6276C>T	p.Gly2092Gly	synonymous_variant	Exon 47 of 47	1		ENSP00000382552.1
CACNA1C	ENST00000682835.1	c.6276C>T	p.Gly2092Gly	synonymous_variant	Exon 47 of 47			ENSP00000507282.1
CACNA1C	ENST00000683482.1	c.6267C>T	p.Gly2089Gly	synonymous_variant	Exon 47 of 47			ENSP00000507169.1
CACNA1C	ENST00000682686.1	c.6243C>T	p.Gly2081Gly	synonymous_variant	Exon 46 of 46			ENSP00000507309.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455208 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723376

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	-0.30
CADD	Benign	14
DANN	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr12-2800224;