rs774402582

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_000719.7(CACNA1C):c.5917C>A(p.Arg1973Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,613,870 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: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

CACNA1C
NM_000719.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.12

Publications

5 publications found

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:

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

ITFG2-AS1 links:

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

CACNA1C-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 12-2688579-C-A is Benign according to our data. Variant chr12-2688579-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 456985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.12 with no splicing effect.

BS2

High AC in GnomAdExome4 at 61 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1C	NM_000719.7 link	c.5917C>A	p.Arg1973Arg	synonymous_variant	Exon 46 of 47	ENST00000399655.6	NP_000710.5
CACNA1C	NM_001167623.2 link	c.5917C>A	p.Arg1973Arg	synonymous_variant	Exon 46 of 47	ENST00000399603.6	NP_001161095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CACNA1C	ENST00000399603.6 link	c.5917C>A	p.Arg1973Arg	synonymous_variant	Exon 46 of 47	5	NM_001167623.2	ENSP00000382512.1
CACNA1C	ENST00000399655.6 link	c.5917C>A	p.Arg1973Arg	synonymous_variant	Exon 46 of 47	1	NM_000719.7	ENSP00000382563.1
CACNA1C	ENST00000682544.1 link	c.6256C>A	p.Arg2086Arg	synonymous_variant	Exon 49 of 50			ENSP00000507184.1
CACNA1C	ENST00000406454.8 link	c.6130C>A	p.Arg2044Arg	synonymous_variant	Exon 47 of 48	5		ENSP00000385896.3
CACNA1C	ENST00000399634.6 link	c.6097C>A	p.Arg2033Arg	synonymous_variant	Exon 46 of 47	5		ENSP00000382542.2
CACNA1C	ENST00000683824.1 link	c.6082C>A	p.Arg2028Arg	synonymous_variant	Exon 47 of 48			ENSP00000507867.1
CACNA1C	ENST00000347598.9 link	c.6061C>A	p.Arg2021Arg	synonymous_variant	Exon 48 of 49	1		ENSP00000266376.6
CACNA1C	ENST00000344100.7 link	c.6040C>A	p.Arg2014Arg	synonymous_variant	Exon 46 of 47	1		ENSP00000341092.3
CACNA1C	ENST00000327702.12 link	c.6022C>A	p.Arg2008Arg	synonymous_variant	Exon 47 of 48	1		ENSP00000329877.7
CACNA1C	ENST00000399617.6 link	c.6022C>A	p.Arg2008Arg	synonymous_variant	Exon 47 of 48	5		ENSP00000382526.1
CACNA1C	ENST00000682462.1 link	c.6007C>A	p.Arg2003Arg	synonymous_variant	Exon 46 of 47			ENSP00000507105.1
CACNA1C	ENST00000683781.1 link	c.6007C>A	p.Arg2003Arg	synonymous_variant	Exon 46 of 47			ENSP00000507434.1
CACNA1C	ENST00000683840.1 link	c.6007C>A	p.Arg2003Arg	synonymous_variant	Exon 46 of 47			ENSP00000507612.1
CACNA1C	ENST00000683956.1 link	c.6007C>A	p.Arg2003Arg	synonymous_variant	Exon 46 of 47			ENSP00000506882.1
CACNA1C	ENST00000399638.5 link	c.6001C>A	p.Arg2001Arg	synonymous_variant	Exon 47 of 48	1		ENSP00000382547.1
CACNA1C	ENST00000335762.10 link	c.5992C>A	p.Arg1998Arg	synonymous_variant	Exon 47 of 48	5		ENSP00000336982.5
CACNA1C	ENST00000399606.5 link	c.5977C>A	p.Arg1993Arg	synonymous_variant	Exon 47 of 48	1		ENSP00000382515.1
CACNA1C	ENST00000399621.5 link	c.5974C>A	p.Arg1992Arg	synonymous_variant	Exon 46 of 47	1		ENSP00000382530.1
CACNA1C	ENST00000399637.5 link	c.5974C>A	p.Arg1992Arg	synonymous_variant	Exon 46 of 47	1		ENSP00000382546.1
CACNA1C	ENST00000402845.7 link	c.5974C>A	p.Arg1992Arg	synonymous_variant	Exon 46 of 47	1		ENSP00000385724.3
CACNA1C	ENST00000399629.5 link	c.5968C>A	p.Arg1990Arg	synonymous_variant	Exon 46 of 47	1		ENSP00000382537.1
CACNA1C	ENST00000682336.1 link	c.5959C>A	p.Arg1987Arg	synonymous_variant	Exon 46 of 47			ENSP00000507898.1
CACNA1C	ENST00000399591.5 link	c.5941C>A	p.Arg1981Arg	synonymous_variant	Exon 45 of 46	1		ENSP00000382500.1
CACNA1C	ENST00000399595.5 link	c.5941C>A	p.Arg1981Arg	synonymous_variant	Exon 45 of 46	1		ENSP00000382504.1
CACNA1C	ENST00000399649.5 link	c.5935C>A	p.Arg1979Arg	synonymous_variant	Exon 45 of 46	1		ENSP00000382557.1
CACNA1C	ENST00000399597.5 link	c.5917C>A	p.Arg1973Arg	synonymous_variant	Exon 46 of 47	1		ENSP00000382506.1
CACNA1C	ENST00000399601.5 link	c.5917C>A	p.Arg1973Arg	synonymous_variant	Exon 46 of 47	1		ENSP00000382510.1
CACNA1C	ENST00000399641.6 link	c.5917C>A	p.Arg1973Arg	synonymous_variant	Exon 46 of 47	1		ENSP00000382549.1
CACNA1C	ENST00000399644.5 link	c.5917C>A	p.Arg1973Arg	synonymous_variant	Exon 46 of 47	1		ENSP00000382552.1
CACNA1C	ENST00000682835.1 link	c.5917C>A	p.Arg1973Arg	synonymous_variant	Exon 46 of 47			ENSP00000507282.1
CACNA1C	ENST00000683482.1 link	c.5908C>A	p.Arg1970Arg	synonymous_variant	Exon 46 of 47			ENSP00000507169.1
CACNA1C	ENST00000682686.1 link	c.5884C>A	p.Arg1962Arg	synonymous_variant	Exon 45 of 46			ENSP00000507309.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000161

AC:

AN:

248464

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000417

AC:

AN:

1461646

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000504

AC:

AN:

1111866

Other (OTH)

AF:

0.0000663

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Long QT syndrome

Benign:1

Oct 31, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Nov 08, 2020

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

5.7

(source)

DANN

Benign

0.63

PhyloP100

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over