rs72552065

Variant names:

• chr12-2679644-C-T
• rs72552065
• NM_000719.7:c.5292C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-2679644-C-T
• chr12-2679644-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000719.7(CACNA1C):​c.5292C>T​(p.Asn1764Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 1,613,704 control chromosomes in the GnomAD database, including 2,891 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (192 hom., cov: 33)
  • Exomes 𝑓: 0.057 (2699 hom.)
• Consequence: CACNA1C NM_000719.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.630
• Publications: 14 publications found

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]

ITFG2-AS1 (HGNC:53128): (ITFG2 antisense RNA 1)

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 12-2679644-C-T is Benign according to our data. Variant chr12-2679644-C-T is described in ClinVar as Benign. ClinVar VariationId is 136633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.63 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000719.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1C	NM_000719.7	MANE Select	c.5292C>T	p.Asn1764Asn	synonymous	Exon 42 of 47	NP_000710.5
	CACNA1C	NM_001167623.2	MANE Plus Clinical	c.5292C>T	p.Asn1764Asn	synonymous	Exon 42 of 47	NP_001161095.1	Q13936-37
	CACNA1C	NM_199460.4		c.5436C>T	p.Asn1812Asn	synonymous	Exon 44 of 50	NP_955630.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1C	ENST00000399603.6	TSL:5 MANE Plus Clinical	c.5292C>T	p.Asn1764Asn	synonymous	Exon 42 of 47	ENSP00000382512.1	Q13936-37
	CACNA1C	ENST00000399655.6	TSL:1 MANE Select	c.5292C>T	p.Asn1764Asn	synonymous	Exon 42 of 47	ENSP00000382563.1	Q13936-12
	CACNA1C	ENST00000682544.1		c.5526C>T	p.Asn1842Asn	synonymous	Exon 44 of 50	ENSP00000507184.1	A0A804HIR0

Frequencies

GnomAD3 genomes AF: 0.0440 AC: 6702 AN: 152204 Hom.: 192 Cov.: 33

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0480

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0494

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0650

Gnomad OTH AF: 0.0463

GnomAD2 exomes AF: 0.0449 AC: 11087 AN: 246974 AF XY: 0.0455

Gnomad AFR exome AF: 0.00946

Gnomad AMR exome AF: 0.0283

Gnomad ASJ exome AF: 0.0941

Gnomad EAS exome AF: 0.000334

Gnomad FIN exome AF: 0.0504

Gnomad NFE exome AF: 0.0648

Gnomad OTH exome AF: 0.0553

GnomAD4 exome AF: 0.0569 AC: 83126 AN: 1461382 Hom.: 2699 Cov.: 32 AF XY: 0.0559 AC XY: 40660 AN XY: 726966

African (AFR) AF: 0.0101 AC: 339 AN: 33474

American (AMR) AF: 0.0299 AC: 1335 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 2352 AN: 26116

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39692

South Asian (SAS) AF: 0.0135 AC: 1160 AN: 86234

European-Finnish (FIN) AF: 0.0522 AC: 2784 AN: 53366

Middle Eastern (MID) AF: 0.0458 AC: 264 AN: 5768

European-Non Finnish (NFE) AF: 0.0644 AC: 71549 AN: 1111676

Other (OTH) AF: 0.0552 AC: 3332 AN: 60362

GnomAD4 genome AF: 0.0440 AC: 6698 AN: 152322 Hom.: 192 Cov.: 33 AF XY: 0.0432 AC XY: 3219 AN XY: 74468

African (AFR) AF: 0.0110 AC: 459 AN: 41580

American (AMR) AF: 0.0479 AC: 732 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0953 AC: 331 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4826

European-Finnish (FIN) AF: 0.0494 AC: 525 AN: 10626

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0650 AC: 4423 AN: 68020

Other (OTH) AF: 0.0458 AC: 97 AN: 2116

Alfa AF: 0.0529 Hom.: 225

Bravo AF: 0.0430

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.0662

EpiControl AF: 0.0651

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.61
DANN	Benign	0.92
PhyloP100		-0.63
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs72552065; hg19: chr12-2788810; COSMIC: COSV59719622; COSMIC: COSV59719622;