Variant 16-1211282-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.4338T>C(p.Ile1446=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 1,612,988 control chromosomes in the GnomAD database, including 553,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55858 hom., cov: 34)

Exomes 𝑓: 0.82 ( 497524 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.120

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 16-1211282-T-C is Benign according to our data. Variant chr16-1211282-T-C is described in ClinVar as [Benign]. Clinvar id is 585644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1211282-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1H	NM_021098.3 linkuse as main transcript	c.4338T>C	p.Ile1446=	synonymous_variant	22/35	ENST00000348261.11	NP_066921.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1H	ENST00000348261.11 linkuse as main transcript	c.4338T>C	p.Ile1446=	synonymous_variant	22/35	1	NM_021098.3	ENSP00000334198	P4	O95180-1

Frequencies

GnomAD3 genomes

AF:

0.854

AC:

130018

AN:

152160

Hom.:

55798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.906

Gnomad AMI

AF:

0.797

Gnomad AMR

AF:

0.861

Gnomad ASJ

AF:

0.885

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.946

Gnomad FIN

AF:

0.860

Gnomad MID

AF:

0.905

Gnomad NFE

AF:

0.802

Gnomad OTH

AF:

0.864

GnomAD3 exomes

AF:

0.860

AC:

213791

AN:

248576

Hom.:

92488

AF XY:

0.861

AC XY:

116306

AN XY:

135106

show subpopulations

Gnomad AFR exome

AF:

0.906

Gnomad AMR exome

AF:

0.872

Gnomad ASJ exome

AF:

0.879

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.941

Gnomad FIN exome

AF:

0.852

Gnomad NFE exome

AF:

0.806

Gnomad OTH exome

AF:

0.849

GnomAD4 exome

AF:

0.824

AC:

1203161

AN:

1460710

Hom.:

497524

Cov.:

AF XY:

0.826

AC XY:

600478

AN XY:

726642

show subpopulations

Gnomad4 AFR exome

AF:

0.915

Gnomad4 AMR exome

AF:

0.868

Gnomad4 ASJ exome

AF:

0.879

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.938

Gnomad4 FIN exome

AF:

0.852

Gnomad4 NFE exome

AF:

0.800

Gnomad4 OTH exome

AF:

0.844

GnomAD4 genome

AF:

0.855

AC:

130138

AN:

152278

Hom.:

55858

Cov.:

AF XY:

0.860

AC XY:

64011

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.907

Gnomad4 AMR

AF:

0.861

Gnomad4 ASJ

AF:

0.885

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.946

Gnomad4 FIN

AF:

0.860

Gnomad4 NFE

AF:

0.802

Gnomad4 OTH

AF:

0.866

Alfa

AF:

0.822

Hom.:

66885

Bravo

AF:

0.855

Asia WGS

AF:

0.969

AC:

3369

AN:

3478

EpiCase

AF:

0.815

EpiControl

AF:

0.808

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 16, 2019	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.4

DANN

Benign

0.54

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