Variant 12-2605138-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_000719.7(CACNA1C):c.3018G>A(p.Leu1006Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,620 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CACNA1C
NM_000719.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.36

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-AS3 (HGNC:40117): (CACNA1C antisense RNA 3)

CACNA1C-AS3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 12-2605138-G-A is Benign according to our data. Variant chr12-2605138-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2908546.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.36 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1C	NM_000719.7 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/47	ENST00000399655.6	NP_000710.5	Q13936-12
CACNA1C	NM_001167623.2 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/47	ENST00000399603.6	NP_001161095.1	Q13936-37

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CACNA1C	ENST00000399603.6 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/47	5	NM_001167623.2	ENSP00000382512.1	Q13936-37
CACNA1C	ENST00000399655.6 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/47	1	NM_000719.7	ENSP00000382563.1	Q13936-12
CACNA1C	ENST00000682544.1 link	c.3168G>A	p.Leu1056Leu	synonymous_variant	24/50			ENSP00000507184.1	A0A804HIR0
CACNA1C	ENST00000406454.8 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/48	5		ENSP00000385896.3	F5GY28
CACNA1C	ENST00000399634.6 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/47	5		ENSP00000382542.2	E9PDI6
CACNA1C	ENST00000683824.1 link	c.3183G>A	p.Leu1061Leu	synonymous_variant	24/48			ENSP00000507867.1	A0A804HKC4
CACNA1C	ENST00000347598.9 link	c.3078G>A	p.Leu1026Leu	synonymous_variant	24/49	1		ENSP00000266376.6	Q13936-11
CACNA1C	ENST00000344100.7 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/47	1		ENSP00000341092.3	Q13936-14
CACNA1C	ENST00000327702.12 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/48	1		ENSP00000329877.7	A0A0A0MR67
CACNA1C	ENST00000399617.6 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/48	5		ENSP00000382526.1	A0A0A0MSA1
CACNA1C	ENST00000682462.1 link	c.3108G>A	p.Leu1036Leu	synonymous_variant	23/47			ENSP00000507105.1	A0A804HIJ8
CACNA1C	ENST00000683781.1 link	c.3108G>A	p.Leu1036Leu	synonymous_variant	23/47			ENSP00000507434.1	A0A804HJB6
CACNA1C	ENST00000683840.1 link	c.3108G>A	p.Leu1036Leu	synonymous_variant	23/47			ENSP00000507612.1	A0A804HJR1
CACNA1C	ENST00000683956.1 link	c.3108G>A	p.Leu1036Leu	synonymous_variant	23/47			ENSP00000506882.1	A0A804HI37
CACNA1C	ENST00000399638.5 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/48	1		ENSP00000382547.1	Q13936-31
CACNA1C	ENST00000335762.10 link	c.3093G>A	p.Leu1031Leu	synonymous_variant	24/48	5		ENSP00000336982.5	F5H522
CACNA1C	ENST00000399606.5 link	c.3078G>A	p.Leu1026Leu	synonymous_variant	24/48	1		ENSP00000382515.1	Q13936-30
CACNA1C	ENST00000399621.5 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/47	1		ENSP00000382530.1	Q13936-24
CACNA1C	ENST00000399637.5 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/47	1		ENSP00000382546.1	Q13936-27
CACNA1C	ENST00000402845.7 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/47	1		ENSP00000385724.3	Q13936-13
CACNA1C	ENST00000399629.5 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/47	1		ENSP00000382537.1	Q13936-32
CACNA1C	ENST00000682336.1 link	c.3093G>A	p.Leu1031Leu	synonymous_variant	24/47			ENSP00000507898.1	A0A804HKE9
CACNA1C	ENST00000399591.5 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/46	1		ENSP00000382500.1	Q13936-29
CACNA1C	ENST00000399595.5 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/46	1		ENSP00000382504.1	Q13936-25
CACNA1C	ENST00000399649.5 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/46	1		ENSP00000382557.1	Q13936-15
CACNA1C	ENST00000399597.5 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/47	1		ENSP00000382506.1	Q13936-22
CACNA1C	ENST00000399601.5 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/47	1		ENSP00000382510.1	Q13936-20
CACNA1C	ENST00000399641.6 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/47	1		ENSP00000382549.1	Q13936-23
CACNA1C	ENST00000399644.5 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/47	1		ENSP00000382552.1	Q13936-21
CACNA1C	ENST00000682835.1 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/47			ENSP00000507282.1	A0A804HIZ0
CACNA1C	ENST00000683482.1 link	c.3009G>A	p.Leu1003Leu	synonymous_variant	23/47			ENSP00000507169.1	Q13936-35
CACNA1C	ENST00000682686.1 link	c.3018G>A	p.Leu1006Leu	synonymous_variant	23/46			ENSP00000507309.1	Q13936-19
CACNA1C	ENST00000480911.6 link	n.*1625G>A		non_coding_transcript_exon_variant	21/27	5		ENSP00000437936.2	F5H638
CACNA1C	ENST00000480911.6 link	n.*1625G>A		3_prime_UTR_variant	21/27	5		ENSP00000437936.2	F5H638

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461408

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727008

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Long QT syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 09, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

8.2

DANN

Benign

0.86

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