rs58893912

Variant names:

• chr12-2668895-C-A
• rs58893912
• NM_000719.7:c.4624-38C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-2668895-C-A
• chr12-2668895-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000719.7(CACNA1C):​c.4624-38C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000395 in 1,421,014 control chromosomes in the GnomAD database, including 1 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 0.0020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: CACNA1C NM_000719.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357
• Publications: 1 publications found

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]

ITFG2-AS1 (HGNC:53128): (ITFG2 antisense RNA 1)

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00204 (311/152258) while in subpopulation AFR AF = 0.00728 (302/41510). AF 95% confidence interval is 0.0066. There are 1 homozygotes in GnomAd4. There are 153 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 311 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1C	NM_000719.7	c.4624-38C>A		intron_variant	Intron 37 of 46	ENST00000399655.6	NP_000710.5
CACNA1C	NM_001167623.2	c.4624-38C>A		intron_variant	Intron 37 of 46	ENST00000399603.6	NP_001161095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1C	ENST00000399603.6	c.4624-38C>A		intron_variant	Intron 37 of 46	5	NM_001167623.2	ENSP00000382512.1
CACNA1C	ENST00000399655.6	c.4624-38C>A		intron_variant	Intron 37 of 46	1	NM_000719.7	ENSP00000382563.1
CACNA1C	ENST00000682544.1	c.4858-38C>A		intron_variant	Intron 39 of 49			ENSP00000507184.1
CACNA1C	ENST00000406454.8	c.4624-38C>A		intron_variant	Intron 37 of 47	5		ENSP00000385896.3
CACNA1C	ENST00000399634.6	c.4591-38C>A		intron_variant	Intron 36 of 46	5		ENSP00000382542.2
CACNA1C	ENST00000683824.1	c.4789-38C>A		intron_variant	Intron 38 of 47			ENSP00000507867.1
CACNA1C	ENST00000347598.9	c.4768-38C>A		intron_variant	Intron 39 of 48	1		ENSP00000266376.6
CACNA1C	ENST00000344100.7	c.4690-38C>A		intron_variant	Intron 37 of 46	1		ENSP00000341092.3
CACNA1C	ENST00000327702.12	c.4624-38C>A		intron_variant	Intron 37 of 47	1		ENSP00000329877.7
CACNA1C	ENST00000399617.6	c.4624-38C>A		intron_variant	Intron 37 of 47	5		ENSP00000382526.1
CACNA1C	ENST00000682462.1	c.4714-38C>A		intron_variant	Intron 37 of 46			ENSP00000507105.1
CACNA1C	ENST00000683781.1	c.4714-38C>A		intron_variant	Intron 37 of 46			ENSP00000507434.1
CACNA1C	ENST00000683840.1	c.4714-38C>A		intron_variant	Intron 37 of 46			ENSP00000507612.1
CACNA1C	ENST00000683956.1	c.4714-38C>A		intron_variant	Intron 37 of 46			ENSP00000506882.1
CACNA1C	ENST00000399638.5	c.4708-38C>A		intron_variant	Intron 38 of 47	1		ENSP00000382547.1
CACNA1C	ENST00000335762.10	c.4699-38C>A		intron_variant	Intron 38 of 47	5		ENSP00000336982.5
CACNA1C	ENST00000399606.5	c.4684-38C>A		intron_variant	Intron 38 of 47	1		ENSP00000382515.1
CACNA1C	ENST00000399621.5	c.4624-38C>A		intron_variant	Intron 37 of 46	1		ENSP00000382530.1
CACNA1C	ENST00000399637.5	c.4624-38C>A		intron_variant	Intron 37 of 46	1		ENSP00000382546.1
CACNA1C	ENST00000402845.7	c.4624-38C>A		intron_variant	Intron 37 of 46	1		ENSP00000385724.3
CACNA1C	ENST00000399629.5	c.4675-38C>A		intron_variant	Intron 37 of 46	1		ENSP00000382537.1
CACNA1C	ENST00000682336.1	c.4666-38C>A		intron_variant	Intron 37 of 46			ENSP00000507898.1
CACNA1C	ENST00000399591.5	c.4591-38C>A		intron_variant	Intron 36 of 45	1		ENSP00000382500.1
CACNA1C	ENST00000399595.5	c.4591-38C>A		intron_variant	Intron 36 of 45	1		ENSP00000382504.1
CACNA1C	ENST00000399649.5	c.4585-38C>A		intron_variant	Intron 36 of 45	1		ENSP00000382557.1
CACNA1C	ENST00000399597.5	c.4624-38C>A		intron_variant	Intron 37 of 46	1		ENSP00000382506.1
CACNA1C	ENST00000399601.5	c.4624-38C>A		intron_variant	Intron 37 of 46	1		ENSP00000382510.1
CACNA1C	ENST00000399641.6	c.4624-38C>A		intron_variant	Intron 37 of 46	1		ENSP00000382549.1
CACNA1C	ENST00000399644.5	c.4624-38C>A		intron_variant	Intron 37 of 46	1		ENSP00000382552.1
CACNA1C	ENST00000682835.1	c.4624-38C>A		intron_variant	Intron 37 of 46			ENSP00000507282.1
CACNA1C	ENST00000683482.1	c.4615-38C>A		intron_variant	Intron 37 of 46			ENSP00000507169.1
CACNA1C	ENST00000682686.1	c.4591-38C>A		intron_variant	Intron 36 of 45			ENSP00000507309.1

Frequencies

GnomAD3 genomes AF: 0.00205 AC: 312 AN: 152140 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00732

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000553 AC: 138 AN: 249364 AF XY: 0.000473

Gnomad AFR exome AF: 0.00774

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.000825

GnomAD4 exome AF: 0.000197 AC: 250 AN: 1268756 Hom.: 0 Cov.: 18 AF XY: 0.000159 AC XY: 102 AN XY: 641072

African (AFR) AF: 0.00701 AC: 208 AN: 29658

American (AMR) AF: 0.000337 AC: 15 AN: 44486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24968

East Asian (EAS) AF: 0.00 AC: 0 AN: 38738

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5400

European-Non Finnish (NFE) AF: 0.00000534 AC: 5 AN: 935826

Other (OTH) AF: 0.000389 AC: 21 AN: 54030

GnomAD4 genome AF: 0.00204 AC: 311 AN: 152258 Hom.: 1 Cov.: 32 AF XY: 0.00205 AC XY: 153 AN XY: 74468

African (AFR) AF: 0.00728 AC: 302 AN: 41510

American (AMR) AF: 0.000523 AC: 8 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000136 Hom.: 15

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.64
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs58893912; hg19: chr12-2778061;