Variant 12-2668886-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000719.7(CACNA1C):c.4624-47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,299,490 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0098 ( 28 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 23 hom. )

Consequence

CACNA1C
NM_000719.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.12

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:

CACNA1C-AS2 (HGNC:40118): (CACNA1C antisense RNA 2)

CACNA1C-AS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 12-2668886-A-G is Benign according to our data. Variant chr12-2668886-A-G is described in ClinVar as [Benign]. Clinvar id is 695632.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0098 (1491/152214) while in subpopulation AFR AF= 0.0341 (1414/41524). AF 95% confidence interval is 0.0326. There are 28 homozygotes in gnomad4. There are 698 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1491 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
CACNA1C	NM_000719.7 linkuse as main transcript	c.4624-47A>G	intron_variant		ENST00000399655.6	NP_000710.5
CACNA1C	NM_001167623.2 linkuse as main transcript	c.4624-47A>G	intron_variant		ENST00000399603.6	NP_001161095.1
CACNA1C-AS2	NR_046579.1 linkuse as main transcript	n.223T>C	non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CACNA1C	ENST00000399603.6 linkuse as main transcript	c.4624-47A>G	intron_variant		5	NM_001167623.2	ENSP00000382512	Q13936-37
CACNA1C	ENST00000399655.6 linkuse as main transcript	c.4624-47A>G	intron_variant		1	NM_000719.7	ENSP00000382563	Q13936-12
CACNA1C-AS2	ENST00000545526.1 linkuse as main transcript	n.223T>C	non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00977

AC:

1486

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0341

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00251

AC:

623

AN:

248632

Hom.:

AF XY:

0.00204

AC XY:

275

AN XY:

134824

show subpopulations

Gnomad AFR exome

AF:

0.0345

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00106

AC:

1218

AN:

1147276

Hom.:

Cov.:

AF XY:

0.000908

AC XY:

532

AN XY:

585822

show subpopulations

Gnomad4 AFR exome

AF:

0.0352

Gnomad4 AMR exome

AF:

0.00183

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000876

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000715

Gnomad4 OTH exome

AF:

0.00213

GnomAD4 genome

AF:

0.00980

AC:

1491

AN:

152214

Hom.:

Cov.:

AF XY:

0.00938

AC XY:

698

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0341

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00182

Hom.:

Bravo

AF:

0.0116

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Long QT syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.77

DANN

Benign

0.52

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