Variant 16-1200559-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021098.3(CACNA1H):c.1107T>C(p.Ile369=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 1,611,322 control chromosomes in the GnomAD database, including 150,941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14162 hom., cov: 33)

Exomes 𝑓: 0.42 ( 136779 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.69

Variant links:

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]

CACNA1H links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-1200559-T-C is Benign according to our data. Variant chr16-1200559-T-C is described in ClinVar as [Benign]. Clinvar id is 166755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1200559-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.69 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1H	NM_021098.3 linkuse as main transcript	c.1107T>C	p.Ile369=	synonymous_variant	7/35	ENST00000348261.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1H	ENST00000348261.11 linkuse as main transcript	c.1107T>C	p.Ile369=	synonymous_variant	7/35	1	NM_021098.3	P4	O95180-1

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

64020

AN:

151904

Hom.:

14133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.492

Gnomad AMI

AF:

0.321

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.497

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.436

Gnomad OTH

AF:

0.385

GnomAD3 exomes

AF:

0.370

AC:

90696

AN:

245158

Hom.:

18348

AF XY:

0.371

AC XY:

49623

AN XY:

133816

show subpopulations

Gnomad AFR exome

AF:

0.489

Gnomad AMR exome

AF:

0.262

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.116

Gnomad SAS exome

AF:

0.312

Gnomad FIN exome

AF:

0.496

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.362

GnomAD4 exome

AF:

0.424

AC:

619188

AN:

1459300

Hom.:

136779

Cov.:

AF XY:

0.420

AC XY:

304849

AN XY:

725992

show subpopulations

Gnomad4 AFR exome

AF:

0.487

Gnomad4 AMR exome

AF:

0.270

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.0844

Gnomad4 SAS exome

AF:

0.313

Gnomad4 FIN exome

AF:

0.491

Gnomad4 NFE exome

AF:

0.453

Gnomad4 OTH exome

AF:

0.392

GnomAD4 genome

AF:

0.422

AC:

64089

AN:

152022

Hom.:

14162

Cov.:

AF XY:

0.417

AC XY:

31000

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.492

Gnomad4 AMR

AF:

0.308

Gnomad4 ASJ

AF:

0.247

Gnomad4 EAS

AF:

0.115

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.497

Gnomad4 NFE

AF:

0.437

Gnomad4 OTH

AF:

0.380

Alfa

AF:

0.393

Hom.:

6585

Bravo

AF:

0.411

Asia WGS

AF:

0.229

AC:

796

AN:

3478

EpiCase

AF:

0.404

EpiControl

AF:

0.408

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 03, 2020	This variant is associated with the following publications: (PMID: 12891677, 17156077) -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 07, 2014

- -

Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.8

DANN

Benign

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over