NM_000719.7:c.477+119988G>C

Variant names:

• chr12-2240418-G-C
• rs4765905
• NM_000719.7:c.477+119988G>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000719.7(CACNA1C):​c.477+119988G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,142 control chromosomes in the GnomAD database, including 10,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.35 (10218 hom., cov: 33)
• Consequence: CACNA1C NM_000719.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.782

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-2240418-G-C is Benign according to our data. Variant chr12-2240418-G-C is described in ClinVar as [Benign]. Clinvar id is 1164893.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1C	NM_000719.7	c.477+119988G>C		intron_variant	Intron 3 of 46	ENST00000399655.6	NP_000710.5
CACNA1C	NM_001167623.2	c.477+119988G>C		intron_variant	Intron 3 of 46	ENST00000399603.6	NP_001161095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1C	ENST00000399603.6	c.477+119988G>C		intron_variant	Intron 3 of 46	5	NM_001167623.2	ENSP00000382512.1
CACNA1C	ENST00000399655.6	c.477+119988G>C		intron_variant	Intron 3 of 46	1	NM_000719.7	ENSP00000382563.1
CACNA1C	ENST00000682544.1	c.567+119988G>C		intron_variant	Intron 3 of 49			ENSP00000507184.1
CACNA1C	ENST00000406454.8	c.477+119988G>C		intron_variant	Intron 3 of 47	5		ENSP00000385896.3
CACNA1C	ENST00000399634.6	c.477+119988G>C		intron_variant	Intron 3 of 46	5		ENSP00000382542.2
CACNA1C	ENST00000683824.1	c.567+119988G>C		intron_variant	Intron 3 of 47			ENSP00000507867.1
CACNA1C	ENST00000347598.9	c.477+119988G>C		intron_variant	Intron 3 of 48	1		ENSP00000266376.6
CACNA1C	ENST00000344100.7	c.477+119988G>C		intron_variant	Intron 3 of 46	1		ENSP00000341092.3
CACNA1C	ENST00000327702.12	c.477+119988G>C		intron_variant	Intron 3 of 47	1		ENSP00000329877.7
CACNA1C	ENST00000399617.6	c.477+119988G>C		intron_variant	Intron 3 of 47	5		ENSP00000382526.1
CACNA1C	ENST00000682462.1	c.567+119988G>C		intron_variant	Intron 3 of 46			ENSP00000507105.1
CACNA1C	ENST00000683781.1	c.567+119988G>C		intron_variant	Intron 3 of 46			ENSP00000507434.1
CACNA1C	ENST00000683840.1	c.567+119988G>C		intron_variant	Intron 3 of 46			ENSP00000507612.1
CACNA1C	ENST00000683956.1	c.567+119988G>C		intron_variant	Intron 3 of 46			ENSP00000506882.1
CACNA1C	ENST00000399638.5	c.477+119988G>C		intron_variant	Intron 3 of 47	1		ENSP00000382547.1
CACNA1C	ENST00000335762.10	c.477+119988G>C		intron_variant	Intron 3 of 47	5		ENSP00000336982.5
CACNA1C	ENST00000399606.5	c.477+119988G>C		intron_variant	Intron 3 of 47	1		ENSP00000382515.1
CACNA1C	ENST00000399621.5	c.477+119988G>C		intron_variant	Intron 3 of 46	1		ENSP00000382530.1
CACNA1C	ENST00000399637.5	c.477+119988G>C		intron_variant	Intron 3 of 46	1		ENSP00000382546.1
CACNA1C	ENST00000402845.7	c.477+119988G>C		intron_variant	Intron 3 of 46	1		ENSP00000385724.3
CACNA1C	ENST00000399629.5	c.477+119988G>C		intron_variant	Intron 3 of 46	1		ENSP00000382537.1
CACNA1C	ENST00000682336.1	c.477+119988G>C		intron_variant	Intron 3 of 46			ENSP00000507898.1
CACNA1C	ENST00000399591.5	c.477+119988G>C		intron_variant	Intron 3 of 45	1		ENSP00000382500.1
CACNA1C	ENST00000399595.5	c.477+119988G>C		intron_variant	Intron 3 of 45	1		ENSP00000382504.1
CACNA1C	ENST00000399649.5	c.477+119988G>C		intron_variant	Intron 3 of 45	1		ENSP00000382557.1
CACNA1C	ENST00000399597.5	c.477+119988G>C		intron_variant	Intron 3 of 46	1		ENSP00000382506.1
CACNA1C	ENST00000399601.5	c.477+119988G>C		intron_variant	Intron 3 of 46	1		ENSP00000382510.1
CACNA1C	ENST00000399641.6	c.477+119988G>C		intron_variant	Intron 3 of 46	1		ENSP00000382549.1
CACNA1C	ENST00000399644.5	c.477+119988G>C		intron_variant	Intron 3 of 46	1		ENSP00000382552.1
CACNA1C	ENST00000682835.1	c.477+119988G>C		intron_variant	Intron 3 of 46			ENSP00000507282.1
CACNA1C	ENST00000683482.1	c.477+119988G>C		intron_variant	Intron 3 of 46			ENSP00000507169.1
CACNA1C	ENST00000682686.1	c.477+119988G>C		intron_variant	Intron 3 of 45			ENSP00000507309.1
CACNA1C	ENST00000682152.1	c.426+119988G>C		intron_variant	Intron 2 of 5			ENSP00000506759.1
CACNA1C	ENST00000480911.6	n.477+119988G>C		intron_variant	Intron 3 of 26	5		ENSP00000437936.2

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53767 AN: 152024 Hom.: 10222 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.0508

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.327

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.354 AC: 53804 AN: 152142 Hom.: 10218 Cov.: 33 AF XY: 0.348 AC XY: 25883 AN XY: 74402

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.0506

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.322

Alfa AF: 0.324 Hom.: 4656

Bravo AF: 0.352

Asia WGS AF: 0.150 AC: 527 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Long QT syndrome Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.62

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: rs4765905; hg19: chr12-2349584;