rs2470411

Positions:

• chr12-2006081-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000354425.4(ENSG00000203593):​n.71+1345C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,174 control chromosomes in the GnomAD database, including 22,931 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 0.54 (22931 hom., cov: 33)
• Consequence: ENST00000354425.4 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1C	XM_006719017.3	c.139+34880C>T		intron_variant			XP_006719080.1
CACNA1C	XM_011521020.3	c.139+34880C>T		intron_variant			XP_011519322.1
CACNA1C	XM_017019926.3	c.140-29431C>T		intron_variant			XP_016875415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000354425.4	n.71+1345C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82633 AN: 152056 Hom.: 22916 Cov.: 33

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.543 AC: 82695 AN: 152174 Hom.: 22931 Cov.: 33 AF XY: 0.541 AC XY: 40231 AN XY: 74386

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.554

Alfa AF: 0.524 Hom.: 4250

Bravo AF: 0.549

Asia WGS AF: 0.488 AC: 1699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.87
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2470411; hg19: chr12-2115247;