rs749123185

Variant names:

• chr12-2115309-C-A
• rs749123185
• NM_000719.7:c.135C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-2115309-C-A
• chr12-2115309-C-G
• chr12-2115309-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000719.7(CACNA1C):​c.135C>A​(p.Thr45Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CACNA1C NM_000719.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.69

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 12-2115309-C-A is Benign according to our data. Variant chr12-2115309-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 389815.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1C	NM_000719.7	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47	ENST00000399655.6	NP_000710.5
CACNA1C	NM_001167623.2	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47	ENST00000399603.6	NP_001161095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1C	ENST00000399603.6	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47	5	NM_001167623.2	ENSP00000382512.1
CACNA1C	ENST00000399655.6	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47	1	NM_000719.7	ENSP00000382563.1
CACNA1C	ENST00000682544.1	c.225C>A	p.Thr75Thr	synonymous_variant	Exon 2 of 50			ENSP00000507184.1
CACNA1C	ENST00000406454.8	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 48	5		ENSP00000385896.3
CACNA1C	ENST00000399634.6	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47	5		ENSP00000382542.2
CACNA1C	ENST00000683824.1	c.225C>A	p.Thr75Thr	synonymous_variant	Exon 2 of 48			ENSP00000507867.1
CACNA1C	ENST00000347598.9	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 49	1		ENSP00000266376.6
CACNA1C	ENST00000344100.7	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47	1		ENSP00000341092.3
CACNA1C	ENST00000327702.12	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 48	1		ENSP00000329877.7
CACNA1C	ENST00000399617.6	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 48	5		ENSP00000382526.1
CACNA1C	ENST00000682462.1	c.225C>A	p.Thr75Thr	synonymous_variant	Exon 2 of 47			ENSP00000507105.1
CACNA1C	ENST00000683781.1	c.225C>A	p.Thr75Thr	synonymous_variant	Exon 2 of 47			ENSP00000507434.1
CACNA1C	ENST00000683840.1	c.225C>A	p.Thr75Thr	synonymous_variant	Exon 2 of 47			ENSP00000507612.1
CACNA1C	ENST00000683956.1	c.225C>A	p.Thr75Thr	synonymous_variant	Exon 2 of 47			ENSP00000506882.1
CACNA1C	ENST00000399638.5	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 48	1		ENSP00000382547.1
CACNA1C	ENST00000335762.10	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 48	5		ENSP00000336982.5
CACNA1C	ENST00000399606.5	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 48	1		ENSP00000382515.1
CACNA1C	ENST00000399621.5	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47	1		ENSP00000382530.1
CACNA1C	ENST00000399637.5	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47	1		ENSP00000382546.1
CACNA1C	ENST00000402845.7	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47	1		ENSP00000385724.3
CACNA1C	ENST00000399629.5	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47	1		ENSP00000382537.1
CACNA1C	ENST00000682336.1	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47			ENSP00000507898.1
CACNA1C	ENST00000399591.5	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 46	1		ENSP00000382500.1
CACNA1C	ENST00000399595.5	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 46	1		ENSP00000382504.1
CACNA1C	ENST00000399649.5	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 46	1		ENSP00000382557.1
CACNA1C	ENST00000399597.5	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47	1		ENSP00000382506.1
CACNA1C	ENST00000399601.5	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47	1		ENSP00000382510.1
CACNA1C	ENST00000399641.6	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47	1		ENSP00000382549.1
CACNA1C	ENST00000399644.5	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47	1		ENSP00000382552.1
CACNA1C	ENST00000682835.1	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47			ENSP00000507282.1
CACNA1C	ENST00000683482.1	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 47			ENSP00000507169.1
CACNA1C	ENST00000682686.1	c.135C>A	p.Thr45Thr	synonymous_variant	Exon 2 of 46			ENSP00000507309.1
CACNA1C	ENST00000682152.1	c.84C>A	p.Thr28Thr	synonymous_variant	Exon 1 of 6			ENSP00000506759.1
CACNA1C	ENST00000480911.6	n.135C>A		non_coding_transcript_exon_variant	Exon 2 of 27	5		ENSP00000437936.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1442118 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 716192

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 10, 2016

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.3
DANN	Benign	0.76

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: rs749123185; hg19: chr12-2224475;