Variant 12-2053536-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000719.7(CACNA1C):c.-27T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,352 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: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CACNA1C
NM_000719.7 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.594

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 12-2053536-T-G is Benign according to our data. Variant chr12-2053536-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 385645.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1C	NM_000719.7 link	c.-27T>G		5_prime_UTR_variant	Exon 1 of 47	ENST00000399655.6	NP_000710.5	Q13936-12
CACNA1C	NM_001167623.2 link	c.-27T>G		5_prime_UTR_variant	Exon 1 of 47	ENST00000399603.6	NP_001161095.1	Q13936-37

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1C	ENST00000399603 link	c.-27T>G	5_prime_UTR_variant	Exon 1 of 47	5	NM_001167623.2	ENSP00000382512.1	Q13936-37
CACNA1C	ENST00000399655 link	c.-27T>G	5_prime_UTR_variant	Exon 1 of 47	1	NM_000719.7	ENSP00000382563.1	Q13936-12
CACNA1C	ENST00000406454 link	c.-27T>G	5_prime_UTR_variant	Exon 1 of 48	5		ENSP00000385896.3	F5GY28
CACNA1C	ENST00000399634 link	c.-27T>G	5_prime_UTR_variant	Exon 1 of 47	5		ENSP00000382542.2	E9PDI6
CACNA1C	ENST00000347598 link	c.-27T>G	5_prime_UTR_variant	Exon 1 of 49	1		ENSP00000266376.6	Q13936-11
CACNA1C	ENST00000327702 link	c.-27T>G	5_prime_UTR_variant	Exon 1 of 48	1		ENSP00000329877.7	A0A0A0MR67
CACNA1C	ENST00000399617 link	c.-27T>G	5_prime_UTR_variant	Exon 1 of 48	5		ENSP00000382526.1	A0A0A0MSA1
CACNA1C	ENST00000335762 link	c.-27T>G	5_prime_UTR_variant	Exon 1 of 48	5		ENSP00000336982.5	F5H522
CACNA1C	ENST00000399641 link	c.-27T>G	5_prime_UTR_variant	Exon 1 of 47	1		ENSP00000382549.1	Q13936-23
CACNA1C	ENST00000682835 link	c.-27T>G	5_prime_UTR_variant	Exon 1 of 47			ENSP00000507282.1	A0A804HIZ0
CACNA1C	ENST00000683482 link	c.-27T>G	5_prime_UTR_variant	Exon 1 of 47			ENSP00000507169.1	Q13936-35
CACNA1C	ENST00000682544.1 link	c.140-61688T>G	intron_variant	Intron 1 of 49			ENSP00000507184.1	A0A804HIR0
CACNA1C	ENST00000683824.1 link	c.140-61688T>G	intron_variant	Intron 1 of 47			ENSP00000507867.1	A0A804HKC4
CACNA1C	ENST00000682462.1 link	c.140-61688T>G	intron_variant	Intron 1 of 46			ENSP00000507105.1	A0A804HIJ8
CACNA1C	ENST00000683781.1 link	c.140-61688T>G	intron_variant	Intron 1 of 46			ENSP00000507434.1	A0A804HJB6
CACNA1C	ENST00000683840.1 link	c.140-61688T>G	intron_variant	Intron 1 of 46			ENSP00000507612.1	A0A804HJR1
CACNA1C	ENST00000683956.1 link	c.140-61688T>G	intron_variant	Intron 1 of 46			ENSP00000506882.1	A0A804HI37
CACNA1C	ENST00000344100.7 link	c.-27T>G	upstream_gene_variant		1		ENSP00000341092.3	Q13936-14
CACNA1C	ENST00000399638.5 link	c.-27T>G	upstream_gene_variant		1		ENSP00000382547.1	Q13936-31
CACNA1C	ENST00000399606.5 link	c.-27T>G	upstream_gene_variant		1		ENSP00000382515.1	Q13936-30
CACNA1C	ENST00000399621.5 link	c.-27T>G	upstream_gene_variant		1		ENSP00000382530.1	Q13936-24
CACNA1C	ENST00000399637.5 link	c.-27T>G	upstream_gene_variant		1		ENSP00000382546.1	Q13936-27
CACNA1C	ENST00000402845.7 link	c.-27T>G	upstream_gene_variant		1		ENSP00000385724.3	Q13936-13
CACNA1C	ENST00000399629.5 link	c.-27T>G	upstream_gene_variant		1		ENSP00000382537.1	Q13936-32
CACNA1C	ENST00000682336.1 link	c.-27T>G	upstream_gene_variant				ENSP00000507898.1	A0A804HKE9
CACNA1C	ENST00000399591.5 link	c.-27T>G	upstream_gene_variant		1		ENSP00000382500.1	Q13936-29
CACNA1C	ENST00000399595.5 link	c.-27T>G	upstream_gene_variant		1		ENSP00000382504.1	Q13936-25
CACNA1C	ENST00000399649.5 link	c.-27T>G	upstream_gene_variant		1		ENSP00000382557.1	Q13936-15
CACNA1C	ENST00000399597.5 link	c.-27T>G	upstream_gene_variant		1		ENSP00000382506.1	Q13936-22
CACNA1C	ENST00000399601.5 link	c.-27T>G	upstream_gene_variant		1		ENSP00000382510.1	Q13936-20
CACNA1C	ENST00000399644.5 link	c.-27T>G	upstream_gene_variant		1		ENSP00000382552.1	Q13936-21
CACNA1C	ENST00000682686.1 link	c.-27T>G	upstream_gene_variant				ENSP00000507309.1	Q13936-19
CACNA1C	ENST00000480911.6 link	n.-27T>G	upstream_gene_variant		5		ENSP00000437936.2	F5H638

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000509

AC:

AN:

196360

Hom.:

AF XY:

0.00

AC XY:

AN XY:

105716

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1424352

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

705594

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.15e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 21, 2016

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.80

Splicing

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