chr12-2668962-C-T

Position:

• chr12-2668962-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000719.7(CACNA1C):​c.4653C>T​(p.Asn1551Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CACNA1C NM_000719.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.80

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 12-2668962-C-T is Benign according to our data. Variant chr12-2668962-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2752807.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.8 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1C	NM_000719.7	c.4653C>T	p.Asn1551Asn	synonymous_variant	38/47	ENST00000399655.6	NP_000710.5
CACNA1C	NM_001167623.2	c.4653C>T	p.Asn1551Asn	synonymous_variant	38/47	ENST00000399603.6	NP_001161095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1C	ENST00000399603.6	c.4653C>T	p.Asn1551Asn	synonymous_variant	38/47	5	NM_001167623.2	ENSP00000382512.1
CACNA1C	ENST00000399655.6	c.4653C>T	p.Asn1551Asn	synonymous_variant	38/47	1	NM_000719.7	ENSP00000382563.1
CACNA1C	ENST00000682544.1	c.4887C>T	p.Asn1629Asn	synonymous_variant	40/50			ENSP00000507184.1
CACNA1C	ENST00000406454.8	c.4653C>T	p.Asn1551Asn	synonymous_variant	38/48	5		ENSP00000385896.3
CACNA1C	ENST00000399634.6	c.4620C>T	p.Asn1540Asn	synonymous_variant	37/47	5		ENSP00000382542.2
CACNA1C	ENST00000683824.1	c.4818C>T	p.Asn1606Asn	synonymous_variant	39/48			ENSP00000507867.1
CACNA1C	ENST00000347598.9	c.4797C>T	p.Asn1599Asn	synonymous_variant	40/49	1		ENSP00000266376.6
CACNA1C	ENST00000344100.7	c.4719C>T	p.Asn1573Asn	synonymous_variant	38/47	1		ENSP00000341092.3
CACNA1C	ENST00000327702.12	c.4653C>T	p.Asn1551Asn	synonymous_variant	38/48	1		ENSP00000329877.7
CACNA1C	ENST00000399617.6	c.4653C>T	p.Asn1551Asn	synonymous_variant	38/48	5		ENSP00000382526.1
CACNA1C	ENST00000682462.1	c.4743C>T	p.Asn1581Asn	synonymous_variant	38/47			ENSP00000507105.1
CACNA1C	ENST00000683781.1	c.4743C>T	p.Asn1581Asn	synonymous_variant	38/47			ENSP00000507434.1
CACNA1C	ENST00000683840.1	c.4743C>T	p.Asn1581Asn	synonymous_variant	38/47			ENSP00000507612.1
CACNA1C	ENST00000683956.1	c.4743C>T	p.Asn1581Asn	synonymous_variant	38/47			ENSP00000506882.1
CACNA1C	ENST00000399638.5	c.4737C>T	p.Asn1579Asn	synonymous_variant	39/48	1		ENSP00000382547.1
CACNA1C	ENST00000335762.10	c.4728C>T	p.Asn1576Asn	synonymous_variant	39/48	5		ENSP00000336982.5
CACNA1C	ENST00000399606.5	c.4713C>T	p.Asn1571Asn	synonymous_variant	39/48	1		ENSP00000382515.1
CACNA1C	ENST00000399621.5	c.4653C>T	p.Asn1551Asn	synonymous_variant	38/47	1		ENSP00000382530.1
CACNA1C	ENST00000399637.5	c.4653C>T	p.Asn1551Asn	synonymous_variant	38/47	1		ENSP00000382546.1
CACNA1C	ENST00000402845.7	c.4653C>T	p.Asn1551Asn	synonymous_variant	38/47	1		ENSP00000385724.3
CACNA1C	ENST00000399629.5	c.4704C>T	p.Asn1568Asn	synonymous_variant	38/47	1		ENSP00000382537.1
CACNA1C	ENST00000682336.1	c.4695C>T	p.Asn1565Asn	synonymous_variant	38/47			ENSP00000507898.1
CACNA1C	ENST00000399591.5	c.4620C>T	p.Asn1540Asn	synonymous_variant	37/46	1		ENSP00000382500.1
CACNA1C	ENST00000399595.5	c.4620C>T	p.Asn1540Asn	synonymous_variant	37/46	1		ENSP00000382504.1
CACNA1C	ENST00000399649.5	c.4614C>T	p.Asn1538Asn	synonymous_variant	37/46	1		ENSP00000382557.1
CACNA1C	ENST00000399597.5	c.4653C>T	p.Asn1551Asn	synonymous_variant	38/47	1		ENSP00000382506.1
CACNA1C	ENST00000399601.5	c.4653C>T	p.Asn1551Asn	synonymous_variant	38/47	1		ENSP00000382510.1
CACNA1C	ENST00000399641.6	c.4653C>T	p.Asn1551Asn	synonymous_variant	38/47	1		ENSP00000382549.1
CACNA1C	ENST00000399644.5	c.4653C>T	p.Asn1551Asn	synonymous_variant	38/47	1		ENSP00000382552.1
CACNA1C	ENST00000682835.1	c.4653C>T	p.Asn1551Asn	synonymous_variant	38/47			ENSP00000507282.1
CACNA1C	ENST00000683482.1	c.4644C>T	p.Asn1548Asn	synonymous_variant	38/47			ENSP00000507169.1
CACNA1C	ENST00000682686.1	c.4620C>T	p.Asn1540Asn	synonymous_variant	37/46			ENSP00000507309.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461782 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Long QT syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Benign	0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-2778128;