rs58632975

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_021098.3(CACNA1H):c.5655G>A(p.Ala1885Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000731 in 1,554,192 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A1885A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00073 ( 1 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.83

Publications

1 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 16-1218419-G-A is Benign according to our data. Variant chr16-1218419-G-A is described in ClinVar as Benign. ClinVar VariationId is 460149.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.83 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000781 (119/152306) while in subpopulation NFE AF = 0.001 (68/68030). AF 95% confidence interval is 0.000808. There are 0 homozygotes in GnomAd4. There are 58 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High AC in GnomAd4 at 119 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.5655G>A	p.Ala1885Ala	synonymous_variant	Exon 33 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.5655G>A	p.Ala1885Ala	synonymous_variant	Exon 33 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6 link	c.5670G>A	p.Ala1890Ala	synonymous_variant	Exon 32 of 34	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1 link	c.5673G>A	p.Ala1891Ala	synonymous_variant	Exon 32 of 34			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.5637G>A	p.Ala1879Ala	synonymous_variant	Exon 32 of 34	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000711450.1 link	c.5670G>A	p.Ala1890Ala	synonymous_variant	Exon 33 of 35			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.5655G>A	p.Ala1885Ala	synonymous_variant	Exon 33 of 35	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000638323.1 link	c.5616G>A	p.Ala1872Ala	synonymous_variant	Exon 33 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000562079.6 link	c.5637G>A	p.Ala1879Ala	synonymous_variant	Exon 32 of 34	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000711438.1 link	c.5598G>A	p.Ala1866Ala	synonymous_variant	Exon 32 of 34			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.5655G>A	p.Ala1885Ala	synonymous_variant	Exon 33 of 36			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.5637G>A	p.Ala1879Ala	synonymous_variant	Exon 32 of 35			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.5655G>A	p.Ala1885Ala	synonymous_variant	Exon 33 of 36			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.5655G>A	p.Ala1885Ala	synonymous_variant	Exon 33 of 35			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.5655G>A	p.Ala1885Ala	synonymous_variant	Exon 33 of 34			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.5655G>A		non_coding_transcript_exon_variant	Exon 33 of 37	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.*1607G>A		non_coding_transcript_exon_variant	Exon 32 of 34	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.*736G>A		non_coding_transcript_exon_variant	Exon 33 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*3506G>A		non_coding_transcript_exon_variant	Exon 33 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.*5099G>A		non_coding_transcript_exon_variant	Exon 31 of 34			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.*629G>A		non_coding_transcript_exon_variant	Exon 34 of 36			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.*514G>A		non_coding_transcript_exon_variant	Exon 33 of 35			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.*1267G>A		non_coding_transcript_exon_variant	Exon 34 of 36			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.*322G>A		non_coding_transcript_exon_variant	Exon 34 of 36			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.*322G>A		non_coding_transcript_exon_variant	Exon 34 of 36			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.5637G>A		non_coding_transcript_exon_variant	Exon 32 of 35			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.5655G>A		non_coding_transcript_exon_variant	Exon 33 of 37			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.5655G>A		non_coding_transcript_exon_variant	Exon 33 of 36			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.*771G>A		non_coding_transcript_exon_variant	Exon 33 of 35			ENSP00000518777.1
CACNA1H	ENST00000637236.3 link	n.*1607G>A		3_prime_UTR_variant	Exon 32 of 34	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.*736G>A		3_prime_UTR_variant	Exon 33 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*3506G>A		3_prime_UTR_variant	Exon 33 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.*5099G>A		3_prime_UTR_variant	Exon 31 of 34			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.*629G>A		3_prime_UTR_variant	Exon 34 of 36			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.*514G>A		3_prime_UTR_variant	Exon 33 of 35			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.*1267G>A		3_prime_UTR_variant	Exon 34 of 36			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.*322G>A		3_prime_UTR_variant	Exon 34 of 36			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.*322G>A		3_prime_UTR_variant	Exon 34 of 36			ENSP00000518765.1
CACNA1H	ENST00000711488.1 link	n.*771G>A		3_prime_UTR_variant	Exon 33 of 35			ENSP00000518777.1

Frequencies

GnomAD3 genomes

AF:

0.000782

AC:

119

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000999

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000854

AC:

137

AN:

160384

AF XY:

0.000846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000320

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000896

Gnomad FIN exome

AF:

0.00449

Gnomad NFE exome

AF:

0.000830

Gnomad OTH exome

AF:

0.000665

GnomAD4 exome

AF:

0.000725

AC:

1017

AN:

1401886

Hom.:

Cov.:

AF XY:

0.000688

AC XY:

476

AN XY:

691832

show subpopulations

African (AFR)

AF:

0.000189

AC:

AN:

31762

American (AMR)

AF:

0.000278

AC:

AN:

36012

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25240

East Asian (EAS)

AF:

0.0000278

AC:

AN:

35966

South Asian (SAS)

AF:

0.00

AC:

AN:

79422

European-Finnish (FIN)

AF:

0.00502

AC:

241

AN:

47972

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.000663

AC:

717

AN:

1081574

Other (OTH)

AF:

0.000721

AC:

AN:

58264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

144

216

288

360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<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:

0.000781

AC:

119

AN:

152306

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41572

American (AMR)

AF:

0.0000654

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00433

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00100

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000447

Hom.:

Bravo

AF:

0.000453

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jan 16, 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

-0.73

CADD

Benign

0.39

(source)

DANN

Benign

0.82

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over