12-2449134-T-C

Position:

chr12-2449134-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000719.7(CACNA1C):c.617+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,502,654 control chromosomes in the GnomAD database, including 49,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5659 hom., cov: 33)

Exomes 𝑓: 0.25 ( 43427 hom. )

Consequence

CACNA1C
NM_000719.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.171

Variant links:

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 links:

ENSG00000285734 (HGNC:):

ENSG00000285734 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 12-2449134-T-C is Benign according to our data. Variant chr12-2449134-T-C is described in ClinVar as [Benign]. Clinvar id is 93421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-2449134-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1C	NM_000719.7 linkuse as main transcript	c.617+19T>C		intron_variant		ENST00000399655.6	NP_000710.5	Q13936-12
CACNA1C	NM_001167623.2 linkuse as main transcript	c.617+19T>C		intron_variant		ENST00000399603.6	NP_001161095.1	Q13936-37

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CACNA1C	ENST00000399603.6 linkuse as main transcript	c.617+19T>C	intron_variant	5	NM_001167623.2	ENSP00000382512.1	Q13936-37
CACNA1C	ENST00000399655.6 linkuse as main transcript	c.617+19T>C	intron_variant	1	NM_000719.7	ENSP00000382563.1	Q13936-12
CACNA1C	ENST00000682544.1 linkuse as main transcript	c.707+19T>C	intron_variant			ENSP00000507184.1	A0A804HIR0
CACNA1C	ENST00000406454.8 linkuse as main transcript	c.617+19T>C	intron_variant	5		ENSP00000385896.3	F5GY28
CACNA1C	ENST00000399634.6 linkuse as main transcript	c.617+19T>C	intron_variant	5		ENSP00000382542.2	E9PDI6
CACNA1C	ENST00000683824.1 linkuse as main transcript	c.707+19T>C	intron_variant			ENSP00000507867.1	A0A804HKC4
CACNA1C	ENST00000347598.9 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000266376.6	Q13936-11
CACNA1C	ENST00000344100.7 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000341092.3	Q13936-14
CACNA1C	ENST00000327702.12 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000329877.7	A0A0A0MR67
CACNA1C	ENST00000399617.6 linkuse as main transcript	c.617+19T>C	intron_variant	5		ENSP00000382526.1	A0A0A0MSA1
CACNA1C	ENST00000682462.1 linkuse as main transcript	c.707+19T>C	intron_variant			ENSP00000507105.1	A0A804HIJ8
CACNA1C	ENST00000683781.1 linkuse as main transcript	c.707+19T>C	intron_variant			ENSP00000507434.1	A0A804HJB6
CACNA1C	ENST00000683840.1 linkuse as main transcript	c.707+19T>C	intron_variant			ENSP00000507612.1	A0A804HJR1
CACNA1C	ENST00000683956.1 linkuse as main transcript	c.707+19T>C	intron_variant			ENSP00000506882.1	A0A804HI37
CACNA1C	ENST00000399638.5 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000382547.1	Q13936-31
CACNA1C	ENST00000335762.10 linkuse as main transcript	c.617+19T>C	intron_variant	5		ENSP00000336982.5	F5H522
CACNA1C	ENST00000399606.5 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000382515.1	Q13936-30
CACNA1C	ENST00000399621.5 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000382530.1	Q13936-24
CACNA1C	ENST00000399637.5 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000382546.1	Q13936-27
CACNA1C	ENST00000402845.7 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000385724.3	Q13936-13
CACNA1C	ENST00000399629.5 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000382537.1	Q13936-32
CACNA1C	ENST00000682336.1 linkuse as main transcript	c.617+19T>C	intron_variant			ENSP00000507898.1	A0A804HKE9
CACNA1C	ENST00000399591.5 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000382500.1	Q13936-29
CACNA1C	ENST00000399595.5 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000382504.1	Q13936-25
CACNA1C	ENST00000399649.5 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000382557.1	Q13936-15
CACNA1C	ENST00000399597.5 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000382506.1	Q13936-22
CACNA1C	ENST00000399601.5 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000382510.1	Q13936-20
CACNA1C	ENST00000399641.6 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000382549.1	Q13936-23
CACNA1C	ENST00000399644.5 linkuse as main transcript	c.617+19T>C	intron_variant	1		ENSP00000382552.1	Q13936-21
CACNA1C	ENST00000682835.1 linkuse as main transcript	c.617+19T>C	intron_variant			ENSP00000507282.1	A0A804HIZ0
CACNA1C	ENST00000683482.1 linkuse as main transcript	c.617+19T>C	intron_variant			ENSP00000507169.1	Q13936-35
CACNA1C	ENST00000682686.1 linkuse as main transcript	c.617+19T>C	intron_variant			ENSP00000507309.1	Q13936-19
CACNA1C	ENST00000682152.1 linkuse as main transcript	c.566+19T>C	intron_variant			ENSP00000506759.1	A0A804HHT8
CACNA1C	ENST00000480911.6 linkuse as main transcript	n.617+19T>C	intron_variant	5		ENSP00000437936.2	F5H638

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

41012

AN:

151784

Hom.:

5648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.250

GnomAD3 exomes

AF:

0.252

AC:

34213

AN:

135580

Hom.:

4413

AF XY:

0.256

AC XY:

18116

AN XY:

70762

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.192

Gnomad ASJ exome

AF:

0.316

Gnomad EAS exome

AF:

0.180

Gnomad SAS exome

AF:

0.306

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.250

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.250

AC:

338274

AN:

1350752

Hom.:

43427

Cov.:

AF XY:

0.252

AC XY:

167406

AN XY:

663050

show subpopulations

Gnomad4 AFR exome

AF:

0.333

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.313

Gnomad4 EAS exome

AF:

0.205

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.243

Gnomad4 NFE exome

AF:

0.247

Gnomad4 OTH exome

AF:

0.252

GnomAD4 genome

AF:

0.270

AC:

41072

AN:

151902

Hom.:

5659

Cov.:

AF XY:

0.270

AC XY:

20032

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.326

Gnomad4 AMR

AF:

0.228

Gnomad4 ASJ

AF:

0.323

Gnomad4 EAS

AF:

0.177

Gnomad4 SAS

AF:

0.306

Gnomad4 FIN

AF:

0.247

Gnomad4 NFE

AF:

0.251

Gnomad4 OTH

AF:

0.254

Alfa

AF:

0.270

Hom.:

1028

Bravo

AF:

0.271

Asia WGS

AF:

0.301

AC:

1044

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2011	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 23, 2013	- -

Timothy syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Long QT syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

7.3

DANN

Benign

0.31

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over