Variant 12-2668895-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000719.7(CACNA1C):c.4624-38C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,420,956 control chromosomes in the GnomAD database, including 2,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.071 ( 1250 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 1067 hom. )

Consequence

CACNA1C
NM_000719.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.357

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-2668895-C-G is Benign according to our data. Variant chr12-2668895-C-G is described in ClinVar as [Benign]. Clinvar id is 1231358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
CACNA1C	NM_000719.7 linkuse as main transcript	c.4624-38C>G	intron_variant		ENST00000399655.6	NP_000710.5
CACNA1C	NM_001167623.2 linkuse as main transcript	c.4624-38C>G	intron_variant		ENST00000399603.6	NP_001161095.1
CACNA1C-AS2	NR_046579.1 linkuse as main transcript	n.214G>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.4624-38C>G	intron_variant		5	NM_001167623.2	ENSP00000382512	Q13936-37
CACNA1C	ENST00000399655.6 linkuse as main transcript	c.4624-38C>G	intron_variant		1	NM_000719.7	ENSP00000382563	Q13936-12
CACNA1C-AS2	ENST00000545526.1 linkuse as main transcript	n.214G>C	non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0707

AC:

10758

AN:

152118

Hom.:

1245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0266

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.0478

GnomAD3 exomes

AF:

0.0183

AC:

4564

AN:

249364

Hom.:

498

AF XY:

0.0137

AC XY:

1850

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.0129

Gnomad ASJ exome

AF:

0.000897

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000966

Gnomad OTH exome

AF:

0.00809

GnomAD4 exome

AF:

0.00782

AC:

9927

AN:

1268722

Hom.:

1067

Cov.:

AF XY:

0.00673

AC XY:

4312

AN XY:

641056

show subpopulations

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.0143

Gnomad4 ASJ exome

AF:

0.00120

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000583

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000590

Gnomad4 OTH exome

AF:

0.0163

GnomAD4 genome

AF:

0.0709

AC:

10788

AN:

152234

Hom.:

1250

Cov.:

AF XY:

0.0687

AC XY:

5113

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.246

Gnomad4 AMR

AF:

0.0265

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00101

Gnomad4 OTH

AF:

0.0473

Alfa

AF:

0.00658

Hom.:

Bravo

AF:

0.0835

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.8

DANN

Benign

0.48

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