16-1154007-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_021098.3(CACNA1H):c.270C>T(p.Arg90Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000712 in 1,404,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R90R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0260

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hyperaldosteronism, familial, type IV
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
childhood absence epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
epilepsy, childhood absence, susceptibility to, 6
Inheritance: AD Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

CACNA1H links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 16-1154007-C-T is Benign according to our data. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1154007-C-T is described in CliVar as Likely_benign. Clinvar id is 1108016.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

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

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.270C>T	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>T	p.Arg90Arg	synonymous_variant	Exon 2 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6 link	c.270C>T	p.Arg90Arg	synonymous_variant	Exon 2 of 34	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1 link	c.270C>T	p.Arg90Arg	synonymous_variant	Exon 2 of 34			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.270C>T	p.Arg90Arg	synonymous_variant	Exon 2 of 34	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000711450.1 link	c.270C>T	p.Arg90Arg	synonymous_variant	Exon 2 of 35			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.270C>T	p.Arg90Arg	synonymous_variant	Exon 2 of 35	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000638323.1 link	c.270C>T	p.Arg90Arg	synonymous_variant	Exon 2 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000562079.6 link	c.270C>T	p.Arg90Arg	synonymous_variant	Exon 2 of 34	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000711438.1 link	c.270C>T	p.Arg90Arg	synonymous_variant	Exon 2 of 34			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.270C>T	p.Arg90Arg	synonymous_variant	Exon 2 of 36			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.270C>T	p.Arg90Arg	synonymous_variant	Exon 2 of 35			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.270C>T	p.Arg90Arg	synonymous_variant	Exon 2 of 36			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.270C>T	p.Arg90Arg	synonymous_variant	Exon 2 of 35			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.270C>T	p.Arg90Arg	synonymous_variant	Exon 2 of 34			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.270C>T		non_coding_transcript_exon_variant	Exon 2 of 37	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.270C>T		non_coding_transcript_exon_variant	Exon 2 of 34	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.270C>T		non_coding_transcript_exon_variant	Exon 2 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.270C>T		non_coding_transcript_exon_variant	Exon 2 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.270C>T		non_coding_transcript_exon_variant	Exon 2 of 34			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.270C>T		non_coding_transcript_exon_variant	Exon 2 of 36			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.270C>T		non_coding_transcript_exon_variant	Exon 2 of 35			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.270C>T		non_coding_transcript_exon_variant	Exon 2 of 36			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.270C>T		non_coding_transcript_exon_variant	Exon 2 of 36			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.270C>T		non_coding_transcript_exon_variant	Exon 2 of 36			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.270C>T		non_coding_transcript_exon_variant	Exon 2 of 35			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.270C>T		non_coding_transcript_exon_variant	Exon 2 of 37			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.270C>T		non_coding_transcript_exon_variant	Exon 2 of 36			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.270C>T		non_coding_transcript_exon_variant	Exon 2 of 35			ENSP00000518777.1

Frequencies

GnomAD3 genomes

AF:

0.00000671

AC:

AN:

148928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000717

AC:

AN:

1256038

Hom.:

Cov.:

AF XY:

0.00000970

AC XY:

AN XY:

618476

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25434

American (AMR)

AF:

0.0000444

AC:

AN:

22498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21162

East Asian (EAS)

AF:

0.00

AC:

AN:

26220

South Asian (SAS)

AF:

0.00

AC:

AN:

66376

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3708

European-Non Finnish (NFE)

AF:

0.00000793

AC:

AN:

1008710

Other (OTH)

AF:

0.00

AC:

AN:

50400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000671

AC:

AN:

148928

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72558

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40466

American (AMR)

AF:

0.00

AC:

AN:

14896

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

4934

South Asian (SAS)

AF:

0.00

AC:

AN:

4690

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9920

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67310

Other (OTH)

AF:

0.00

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

Benign:1

Sep 05, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.54

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

-0.026

PromoterAI

0.064

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over