16-1211222-A-G

Variant names:

Variant summary

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

The NM_021098.3(CACNA1H):c.4278A>G(p.Ser1426Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,612,144 control chromosomes in the GnomAD database, including 304,915 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33517 hom., cov: 34)

Exomes 𝑓: 0.61 ( 271398 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.54

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=-0.88).

BP6

Variant 16-1211222-A-G is Benign according to our data. Variant chr16-1211222-A-G is described in ClinVar as [Benign]. Clinvar id is 585643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1211222-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.4278A>G	p.Ser1426Ser	synonymous_variant	Exon 22 of 35	ENST00000348261.11	NP_066921.2	O95180-1B3KQH9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1H	ENST00000348261.11 link	c.4278A>G	p.Ser1426Ser	synonymous_variant	Exon 22 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000565831.6 link	c.4278A>G	p.Ser1426Ser	synonymous_variant	Exon 21 of 33	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000638323.1 link	c.4239A>G	p.Ser1413Ser	synonymous_variant	Exon 22 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000569107.5 link	c.501A>G	p.Ser167Ser	synonymous_variant	Exon 5 of 17	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000564231.5 link	c.501A>G	p.Ser167Ser	synonymous_variant	Exon 5 of 18	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000562079.5 link	c.501A>G	p.Ser167Ser	synonymous_variant	Exon 5 of 17	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000637236.2 link	n.*248A>G		non_coding_transcript_exon_variant	Exon 6 of 6	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.4278A>G		non_coding_transcript_exon_variant	Exon 22 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*2191A>G		non_coding_transcript_exon_variant	Exon 22 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000637236.2 link	n.*248A>G		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000640028.1 link	n.*2191A>G		3_prime_UTR_variant	Exon 22 of 35	5		ENSP00000491488.1	A0A1W2PQ19

Frequencies

GnomAD3 genomes

AF:

0.658

AC:

99933

AN:

151876

Hom.:

33488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.733

Gnomad AMI

AF:

0.571

Gnomad AMR

AF:

0.700

Gnomad ASJ

AF:

0.706

Gnomad EAS

AF:

0.879

Gnomad SAS

AF:

0.570

Gnomad FIN

AF:

0.710

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.660

GnomAD3 exomes

AF:

0.652

AC:

162023

AN:

248452

Hom.:

54010

AF XY:

0.641

AC XY:

86570

AN XY:

135074

show subpopulations

Gnomad AFR exome

AF:

0.736

Gnomad AMR exome

AF:

0.739

Gnomad ASJ exome

AF:

0.690

Gnomad EAS exome

AF:

0.892

Gnomad SAS exome

AF:

0.566

Gnomad FIN exome

AF:

0.696

Gnomad NFE exome

AF:

0.588

Gnomad OTH exome

AF:

0.641

GnomAD4 exome

AF:

0.605

AC:

883958

AN:

1460150

Hom.:

271398

Cov.:

AF XY:

0.603

AC XY:

438145

AN XY:

726402

show subpopulations

Gnomad4 AFR exome

AF:

0.743

Gnomad4 AMR exome

AF:

0.732

Gnomad4 ASJ exome

AF:

0.692

Gnomad4 EAS exome

AF:

0.902

Gnomad4 SAS exome

AF:

0.571

Gnomad4 FIN exome

AF:

0.690

Gnomad4 NFE exome

AF:

0.581

Gnomad4 OTH exome

AF:

0.628

GnomAD4 genome

AF:

0.658

AC:

100007

AN:

151994

Hom.:

33517

Cov.:

AF XY:

0.665

AC XY:

49444

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.732

Gnomad4 AMR

AF:

0.700

Gnomad4 ASJ

AF:

0.706

Gnomad4 EAS

AF:

0.878

Gnomad4 SAS

AF:

0.569

Gnomad4 FIN

AF:

0.710

Gnomad4 NFE

AF:

0.583

Gnomad4 OTH

AF:

0.665

Alfa

AF:

0.606

Hom.:

35187

Bravo

AF:

0.667

Asia WGS

AF:

0.730

AC:

2537

AN:

3478

EpiCase

AF:

0.599

EpiControl

AF:

0.588

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 16, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.073

DANN

Benign

0.53

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