12-2019816-G-T

Variant summary

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

The ENST00000542984.1(CACNA1C-IT1):n.81-110G>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 0.854 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-IT1 ENST00000542984.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442

Genes affected

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

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1C-IT1	XR_001749433.2	n.1623-110G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1C-IT1	ENST00000542984.1	n.81-110G>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.926

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.856

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.843

Alfa AF: 0.837 Hom.: 71374

Bravo AF: 0.860

Asia WGS AF: 0.923 AC: 3206 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	5.3
Dann	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs725779; hg19: chr12-2128982;