rs745571869

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The NM_021098.3(CACNA1H):c.790A>G(p.Ser264Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,396 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 Benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CACNA1H
NM_021098.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.39

Publications

2 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: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29217649).

BP6

Variant 16-1198761-A-G is Benign according to our data. Variant chr16-1198761-A-G is described in ClinVar as Benign. ClinVar VariationId is 460187.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.790A>G	p.Ser264Gly	missense_variant	Exon 6 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.790A>G	p.Ser264Gly	missense_variant	Exon 6 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6 link	c.790A>G	p.Ser264Gly	missense_variant	Exon 6 of 34	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1 link	c.790A>G	p.Ser264Gly	missense_variant	Exon 6 of 34			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.790A>G	p.Ser264Gly	missense_variant	Exon 6 of 34	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000711450.1 link	c.790A>G	p.Ser264Gly	missense_variant	Exon 6 of 35			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.790A>G	p.Ser264Gly	missense_variant	Exon 6 of 35	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000638323.1 link	c.751A>G	p.Ser251Gly	missense_variant	Exon 6 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000562079.6 link	c.790A>G	p.Ser264Gly	missense_variant	Exon 6 of 34	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000711438.1 link	c.751A>G	p.Ser251Gly	missense_variant	Exon 6 of 34			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.790A>G	p.Ser264Gly	missense_variant	Exon 6 of 36			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.790A>G	p.Ser264Gly	missense_variant	Exon 6 of 35			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.790A>G	p.Ser264Gly	missense_variant	Exon 6 of 36			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.790A>G	p.Ser264Gly	missense_variant	Exon 6 of 35			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.790A>G	p.Ser264Gly	missense_variant	Exon 6 of 34			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.790A>G		non_coding_transcript_exon_variant	Exon 6 of 37	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.790A>G		non_coding_transcript_exon_variant	Exon 6 of 34	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.790A>G		non_coding_transcript_exon_variant	Exon 6 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.790A>G		non_coding_transcript_exon_variant	Exon 6 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.*237A>G		non_coding_transcript_exon_variant	Exon 5 of 34			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.790A>G		non_coding_transcript_exon_variant	Exon 6 of 36			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.790A>G		non_coding_transcript_exon_variant	Exon 6 of 35			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.790A>G		non_coding_transcript_exon_variant	Exon 6 of 36			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.790A>G		non_coding_transcript_exon_variant	Exon 6 of 36			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.790A>G		non_coding_transcript_exon_variant	Exon 6 of 36			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.790A>G		non_coding_transcript_exon_variant	Exon 6 of 35			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.790A>G		non_coding_transcript_exon_variant	Exon 6 of 37			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.790A>G		non_coding_transcript_exon_variant	Exon 6 of 36			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.790A>G		non_coding_transcript_exon_variant	Exon 6 of 35			ENSP00000518777.1
CACNA1H	ENST00000711442.1 link	n.*237A>G		3_prime_UTR_variant	Exon 5 of 34			ENSP00000518758.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000407

AC:

AN:

245520

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000562

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459396

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726008

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111246

Other (OTH)

AF:

0.00

AC:

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: 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

Mar 08, 2023

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

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.53

D;.;.;.

Eigen

Benign

-0.0023

Eigen_PC

Benign

-0.0070

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.66

T;T;T;.

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Uncertain

0.42

MutationAssessor

Benign

0.32

N;.;N;N

PhyloP100

1.4

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.9

N;.;N;N

REVEL

Uncertain

0.38

Sift

Uncertain

0.028

D;.;D;D

Sift4G

Benign

0.075

T;.;T;T

Polyphen

0.96

D;.;B;B

Vest4

0.55

MutPred

0.53

Loss of catalytic residue at S264 (P = 0.1216);.;Loss of catalytic residue at S264 (P = 0.1216);Loss of catalytic residue at S264 (P = 0.1216);

MVP

0.89

ClinPred

0.24

GERP RS

3.6

Varity_R

0.17

gMVP

0.76

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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