rs2745167

chr16-1205545-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021098.3(CACNA1H):c.2603+280T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,150 control chromosomes in the GnomAD database, including 14,692 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (14692 hom., cov: 34)
• Consequence: CACNA1H NM_021098.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.196

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-1205545-T-C is Benign according to our data. Variant chr16-1205545-T-C is described in ClinVar as [Benign]. Clinvar id is 1296140.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1H	NM_021098.3	c.2603+280T>C		intron_variant		ENST00000348261.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1H	ENST00000348261.11	c.2603+280T>C		intron_variant		1	NM_021098.3	P4

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64455 AN: 152032 Hom.: 14667 Cov.: 34

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0702

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.424 AC: 64520 AN: 152150 Hom.: 14692 Cov.: 34 AF XY: 0.419 AC XY: 31182 AN XY: 74394

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.0698

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.386

Alfa AF: 0.470 Hom.: 19515

Bravo AF: 0.405

Asia WGS AF: 0.219 AC: 765 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 22, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.8
Dann	Benign	0.63

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: rs2745167; hg19: chr16-1255545;