12-2019816-G-T

Variant names:

• chr12-2019816-G-T
• rs725779
• ENST00000682544.1:c.139+48615G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000682544.1(CACNA1C):​c.139+48615G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,122 control chromosomes in the GnomAD database, including 55,799 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 0.85 (55799 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: CACNA1C ENST00000682544.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442
• Publications: 3 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]

CACNA1C-IT1 (HGNC:41312): (CACNA1C intronic transcript 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000682544.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1C	ENST00000682544.1		c.139+48615G>T		intron	N/A	ENSP00000507184.1
	CACNA1C	ENST00000683824.1		c.139+48615G>T		intron	N/A	ENSP00000507867.1
	CACNA1C	ENST00000682462.1		c.139+48615G>T		intron	N/A	ENSP00000507105.1

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129816 AN: 152004 Hom.: 55749 Cov.: 31

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.879

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.842

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.854 AC: 129923 AN: 152122 Hom.: 55799 Cov.: 31 AF XY: 0.851 AC XY: 63277 AN XY: 74358

African (AFR) AF: 0.926 AC: 38460 AN: 41526

American (AMR) AF: 0.802 AC: 12267 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2929 AN: 3472

East Asian (EAS) AF: 0.985 AC: 5097 AN: 5172

South Asian (SAS) AF: 0.856 AC: 4119 AN: 4812

European-Finnish (FIN) AF: 0.758 AC: 7996 AN: 10550

Middle Eastern (MID) AF: 0.877 AC: 256 AN: 292

European-Non Finnish (NFE) AF: 0.827 AC: 56226 AN: 67980

Other (OTH) AF: 0.843 AC: 1783 AN: 2114

Alfa AF: 0.838 Hom.: 88921

Bravo AF: 0.860

Asia WGS AF: 0.923 AC: 3206 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.3
DANN	Benign	0.44
PhyloP100		0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs725779; hg19: chr12-2128982;