Variant rs371167728 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021098.3(CACNA1H):c.2215C>G(p.Arg739Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CACNA1H
NM_021098.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.117

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.082894385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.2215C>G	p.Arg739Gly	missense_variant	10/35	ENST00000348261.11	NP_066921.2	O95180-1B3KQH9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CACNA1H	ENST00000348261.11 link	c.2215C>G	p.Arg739Gly	missense_variant	10/35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000565831.6 link	c.2215C>G	p.Arg739Gly	missense_variant	9/33	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000638323.1 link	c.2176C>G	p.Arg726Gly	missense_variant	10/35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000639478.1 link	n.2215C>G		non_coding_transcript_exon_variant	10/35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*128C>G		non_coding_transcript_exon_variant	10/35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000640028.1 link	n.*128C>G		3_prime_UTR_variant	10/35	5		ENSP00000491488.1	A0A1W2PQ19

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459378

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725954

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.15

T;.;.;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.63

T;T;T;.

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.083

T;T;T;T

MetaSVM

Uncertain

0.011

MutationAssessor

Benign

1.4

L;.;L;L

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

N;.;N;N

REVEL

Benign

0.16

Sift

Benign

0.38

T;.;T;T

Sift4G

Benign

0.47

T;.;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.26

MutPred

0.36

Loss of MoRF binding (P = 0.038);.;Loss of MoRF binding (P = 0.038);Loss of MoRF binding (P = 0.038);

MVP

0.68

ClinPred

0.37

GERP RS

2.2

Varity_R

0.079

gMVP

0.27

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over