chr16-1154007-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021098.3(CACNA1H):c.270C>G(p.Arg90Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,404,994 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 8 hom., cov: 30)

Exomes 𝑓: 0.0041 ( 79 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0260

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=-0.6).

BP6

Variant 16-1154007-C-G is Benign according to our data. Variant chr16-1154007-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 460071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1154007-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.026 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00353 (526/148996) while in subpopulation SAS AF= 0.0313 (146/4672). AF 95% confidence interval is 0.0271. There are 8 homozygotes in gnomad4. There are 297 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 526 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 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.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000565831.6 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 1 of 33	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000638323.1 link	c.270C>G	p.Arg90Arg	synonymous_variant	Exon 2 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000639478.1 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.270C>G		non_coding_transcript_exon_variant	Exon 2 of 35	5		ENSP00000491488.1	A0A1W2PQ19

Frequencies

GnomAD3 genomes

AF:

0.00354

AC:

527

AN:

148924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000470

Gnomad AMI

AF:

0.00996

Gnomad AMR

AF:

0.00154

Gnomad ASJ

AF:

0.000581

Gnomad EAS

AF:

0.000203

Gnomad SAS

AF:

0.0311

Gnomad FIN

AF:

0.00827

Gnomad MID

AF:

0.00645

Gnomad NFE

AF:

0.00349

Gnomad OTH

AF:

0.00389

GnomAD3 exomes

AF:

0.00962

AC:

695

AN:

72236

Hom.:

AF XY:

0.0126

AC XY:

528

AN XY:

41978

show subpopulations

Gnomad AFR exome

AF:

0.000843

Gnomad AMR exome

AF:

0.00224

Gnomad ASJ exome

AF:

0.000471

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0330

Gnomad FIN exome

AF:

0.00666

Gnomad NFE exome

AF:

0.00353

Gnomad OTH exome

AF:

0.00942

GnomAD4 exome

AF:

0.00407

AC:

5118

AN:

1255998

Hom.:

Cov.:

AF XY:

0.00500

AC XY:

3092

AN XY:

618446

show subpopulations

Gnomad4 AFR exome

AF:

0.000315

Gnomad4 AMR exome

AF:

0.00293

Gnomad4 ASJ exome

AF:

0.000284

Gnomad4 EAS exome

AF:

0.0000381

Gnomad4 SAS exome

AF:

0.0320

Gnomad4 FIN exome

AF:

0.00549

Gnomad4 NFE exome

AF:

0.00242

Gnomad4 OTH exome

AF:

0.00468

GnomAD4 genome

AF:

0.00353

AC:

526

AN:

148996

Hom.:

Cov.:

AF XY:

0.00409

AC XY:

297

AN XY:

72638

show subpopulations

Gnomad4 AFR

AF:

0.000468

Gnomad4 AMR

AF:

0.00154

Gnomad4 ASJ

AF:

0.000581

Gnomad4 EAS

AF:

0.000203

Gnomad4 SAS

AF:

0.0313

Gnomad4 FIN

AF:

0.00827

Gnomad4 NFE

AF:

0.00349

Gnomad4 OTH

AF:

0.00338

Alfa

AF:

0.00239

Hom.:

Bravo

AF:

0.00213

Asia WGS

AF:

0.00850

AC:

AN:

3306

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 07, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 08, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Epilepsy, childhood absence, susceptibility to, 6;C4310756:Hyperaldosteronism, familial, type IV

Benign:1

Aug 04, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Jan 20, 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

-0.60

CADD

Benign

DANN

Benign

0.73

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