dbSNP rs2238092: CACNA1C:c.3828+2087G>A (chr12-2614100-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000719.7(CACNA1C):c.3828+2087G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,054 control chromosomes in the GnomAD database, including 33,668 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.64 ( 33662 hom., cov: 31)

Exomes 𝑓: 0.80 ( 6 hom. )

Consequence

CACNA1C
NM_000719.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.54

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1C	NM_000719.7 link	c.3828+2087G>A		intron_variant	Intron 29 of 46	ENST00000399655.6	NP_000710.5	Q13936-12
CACNA1C	NM_001167623.2 link	c.3828+2087G>A		intron_variant	Intron 29 of 46	ENST00000399603.6	NP_001161095.1	Q13936-37

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1C	ENST00000399603.6 link	c.3828+2087G>A	intron_variant	Intron 29 of 46	5	NM_001167623.2	ENSP00000382512.1	Q13936-37
CACNA1C	ENST00000399655.6 link	c.3828+2087G>A	intron_variant	Intron 29 of 46	1	NM_000719.7	ENSP00000382563.1	Q13936-12
CACNA1C	ENST00000682544.1 link	c.3978+2087G>A	intron_variant	Intron 30 of 49			ENSP00000507184.1	A0A804HIR0
CACNA1C	ENST00000406454.8 link	c.3828+2087G>A	intron_variant	Intron 29 of 47	5		ENSP00000385896.3	F5GY28
CACNA1C	ENST00000399634.6 link	c.3828+2087G>A	intron_variant	Intron 29 of 46	5		ENSP00000382542.2	E9PDI6
CACNA1C	ENST00000683824.1 link	c.3993+2087G>A	intron_variant	Intron 30 of 47			ENSP00000507867.1	A0A804HKC4
CACNA1C	ENST00000347598.9 link	c.3888+2087G>A	intron_variant	Intron 30 of 48	1		ENSP00000266376.6	Q13936-11
CACNA1C	ENST00000344100.7 link	c.3828+2087G>A	intron_variant	Intron 29 of 46	1		ENSP00000341092.3	Q13936-14
CACNA1C	ENST00000327702.12 link	c.3828+2087G>A	intron_variant	Intron 29 of 47	1		ENSP00000329877.7	A0A0A0MR67
CACNA1C	ENST00000399617.6 link	c.3828+2087G>A	intron_variant	Intron 29 of 47	5		ENSP00000382526.1	A0A0A0MSA1
CACNA1C	ENST00000682462.1 link	c.3918+2087G>A	intron_variant	Intron 29 of 46			ENSP00000507105.1	A0A804HIJ8
CACNA1C	ENST00000683781.1 link	c.3918+2087G>A	intron_variant	Intron 29 of 46			ENSP00000507434.1	A0A804HJB6
CACNA1C	ENST00000683840.1 link	c.3918+2087G>A	intron_variant	Intron 29 of 46			ENSP00000507612.1	A0A804HJR1
CACNA1C	ENST00000683956.1 link	c.3918+2087G>A	intron_variant	Intron 29 of 46			ENSP00000506882.1	A0A804HI37
CACNA1C	ENST00000399638.5 link	c.3828+2087G>A	intron_variant	Intron 29 of 47	1		ENSP00000382547.1	Q13936-31
CACNA1C	ENST00000335762.10 link	c.3903+2087G>A	intron_variant	Intron 30 of 47	5		ENSP00000336982.5	F5H522
CACNA1C	ENST00000399606.5 link	c.3888+2087G>A	intron_variant	Intron 30 of 47	1		ENSP00000382515.1	Q13936-30
CACNA1C	ENST00000399621.5 link	c.3828+2087G>A	intron_variant	Intron 29 of 46	1		ENSP00000382530.1	Q13936-24
CACNA1C	ENST00000399637.5 link	c.3828+2087G>A	intron_variant	Intron 29 of 46	1		ENSP00000382546.1	Q13936-27
CACNA1C	ENST00000402845.7 link	c.3828+2087G>A	intron_variant	Intron 29 of 46	1		ENSP00000385724.3	Q13936-13
CACNA1C	ENST00000399629.5 link	c.3828+2087G>A	intron_variant	Intron 29 of 46	1		ENSP00000382537.1	Q13936-32
CACNA1C	ENST00000682336.1 link	c.3903+2087G>A	intron_variant	Intron 30 of 46			ENSP00000507898.1	A0A804HKE9
CACNA1C	ENST00000399591.5 link	c.3828+2087G>A	intron_variant	Intron 29 of 45	1		ENSP00000382500.1	Q13936-29
CACNA1C	ENST00000399595.5 link	c.3828+2087G>A	intron_variant	Intron 29 of 45	1		ENSP00000382504.1	Q13936-25
CACNA1C	ENST00000399649.5 link	c.3828+2087G>A	intron_variant	Intron 29 of 45	1		ENSP00000382557.1	Q13936-15
CACNA1C	ENST00000399597.5 link	c.3828+2087G>A	intron_variant	Intron 29 of 46	1		ENSP00000382506.1	Q13936-22
CACNA1C	ENST00000399601.5 link	c.3828+2087G>A	intron_variant	Intron 29 of 46	1		ENSP00000382510.1	Q13936-20
CACNA1C	ENST00000399641.6 link	c.3828+2087G>A	intron_variant	Intron 29 of 46	1		ENSP00000382549.1	Q13936-23
CACNA1C	ENST00000399644.5 link	c.3828+2087G>A	intron_variant	Intron 29 of 46	1		ENSP00000382552.1	Q13936-21
CACNA1C	ENST00000682835.1 link	c.3828+2087G>A	intron_variant	Intron 29 of 46			ENSP00000507282.1	A0A804HIZ0
CACNA1C	ENST00000683482.1 link	c.3819+2087G>A	intron_variant	Intron 29 of 46			ENSP00000507169.1	Q13936-35
CACNA1C	ENST00000682686.1 link	c.3828+2087G>A	intron_variant	Intron 29 of 45			ENSP00000507309.1	Q13936-19
CACNA1C	ENST00000480911.6 link	n.*4522G>A	non_coding_transcript_exon_variant	Exon 27 of 27	5		ENSP00000437936.2	F5H638
CACNA1C	ENST00000480911.6 link	n.*4522G>A	3_prime_UTR_variant	Exon 27 of 27	5		ENSP00000437936.2	F5H638

Frequencies

GnomAD3 genomes

AF:

0.641

AC:

97396

AN:

151914

Hom.:

33654

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.711

Gnomad AMR

AF:

0.679

Gnomad ASJ

AF:

0.706

Gnomad EAS

AF:

0.654

Gnomad SAS

AF:

0.690

Gnomad FIN

AF:

0.769

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.772

Gnomad OTH

AF:

0.644

GnomAD4 exome

AF:

0.800

AC:

AN:

Hom.:

Cov.:

AF XY:

0.800

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.778

GnomAD4 genome

AF:

0.641

AC:

97435

AN:

152034

Hom.:

33662

Cov.:

AF XY:

0.642

AC XY:

47679

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.365

Gnomad4 AMR

AF:

0.679

Gnomad4 ASJ

AF:

0.706

Gnomad4 EAS

AF:

0.654

Gnomad4 SAS

AF:

0.689

Gnomad4 FIN

AF:

0.769

Gnomad4 NFE

AF:

0.772

Gnomad4 OTH

AF:

0.645

Alfa

AF:

0.736

Hom.:

58877

Bravo

AF:

0.624

Asia WGS

AF:

0.694

AC:

2411

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.049

DANN

Benign

0.63

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over