rs79398153

chr12-2185990-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000719.7(CACNA1C):c.477+65560C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 152,272 control chromosomes in the GnomAD database, including 37 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 0.017 (37 hom., cov: 32)
• Consequence: CACNA1C NM_000719.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0168 (2558/152272) while in subpopulation AMR AF= 0.0352 (539/15296). AF 95% confidence interval is 0.0328. There are 37 homozygotes in gnomad4. There are 1239 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 2559 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1C	NM_000719.7	c.477+65560C>T		intron_variant		ENST00000399655.6
CACNA1C	NM_001167623.2	c.477+65560C>T		intron_variant		ENST00000399603.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1C	ENST00000399603.6	c.477+65560C>T		intron_variant		5	NM_001167623.2
CACNA1C	ENST00000399655.6	c.477+65560C>T		intron_variant		1	NM_000719.7

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2559 AN: 152154 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.00567

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0202

Gnomad OTH AF: 0.0168

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

GnomAD4 genome AF: 0.0168 AC: 2558 AN: 152272 Hom.: 37 Cov.: 32 AF XY: 0.0166 AC XY: 1239 AN XY: 74468

Gnomad4 AFR AF: 0.00565

Gnomad4 AMR AF: 0.0352

Gnomad4 ASJ AF: 0.0447

Gnomad4 EAS AF: 0.0120

Gnomad4 SAS AF: 0.00767

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0202

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0173 Hom.: 4

Bravo AF: 0.0194

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.4
Dann	Benign	0.62

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

Other links and lift over

dbSNP: rs79398153; hg19: chr12-2295156;