rs11640796

chr16-1175628-A-G

Variant summary

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

The NM_021098.3(CACNA1H):c.300-19344A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,082 control chromosomes in the GnomAD database, including 2,865 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 0.16 (2865 hom., cov: 33)
• Consequence: CACNA1H NM_021098.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.91

Genes affected

CACNA1H (HGNC:1395): (calcium voltage-gated channel subunit alpha1 H) This gene encodes a T-type member of the alpha-1 subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. The alpha-1 subunit has 24 transmembrane segments and forms the pore through which ions pass into the cell. There are multiple isoforms of each of the proteins in the complex, either encoded by different genes or the result of alternative splicing of transcripts. Alternate transcriptional splice variants, encoding different isoforms, have been characterized for the gene described here. Studies suggest certain mutations in this gene lead to childhood absence epilepsy (CAE). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1H	NM_021098.3	c.300-19344A>G		intron_variant		ENST00000348261.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1H	ENST00000348261.11	c.300-19344A>G		intron_variant		1	NM_021098.3	P4

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24151 AN: 151962 Hom.: 2864 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.159 AC: 24153 AN: 152082 Hom.: 2865 Cov.: 33 AF XY: 0.169 AC XY: 12549 AN XY: 74346

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.143

Alfa AF: 0.142 Hom.: 2249

Bravo AF: 0.146

Asia WGS AF: 0.391 AC: 1359 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	0.075
Dann	Benign	0.15

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: rs11640796; hg19: chr16-1225628; COSMIC: COSV62002077;