rs57606792

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021098.3(CACNA1H):c.3261C>A(p.Thr1087Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000912 in 1,594,188 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1087T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00093 ( 1 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -5.32

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 16-1208119-C-A is Benign according to our data. Variant chr16-1208119-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 529683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.32 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000696 (106/152304) while in subpopulation NFE AF = 0.00112 (76/68028). AF 95% confidence interval is 0.000915. There are 0 homozygotes in GnomAd4. There are 52 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 106 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.3261C>A	p.Thr1087Thr	synonymous_variant	Exon 16 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.3261C>A	p.Thr1087Thr	synonymous_variant	Exon 16 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6 link	c.3261C>A	p.Thr1087Thr	synonymous_variant	Exon 16 of 34	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1 link	c.3261C>A	p.Thr1087Thr	synonymous_variant	Exon 16 of 34			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.3261C>A	p.Thr1087Thr	synonymous_variant	Exon 16 of 34	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000711450.1 link	c.3261C>A	p.Thr1087Thr	synonymous_variant	Exon 16 of 35			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.3261C>A	p.Thr1087Thr	synonymous_variant	Exon 16 of 35	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000638323.1 link	c.3222C>A	p.Thr1074Thr	synonymous_variant	Exon 16 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000562079.6 link	c.3261C>A	p.Thr1087Thr	synonymous_variant	Exon 16 of 34	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000711438.1 link	c.3222C>A	p.Thr1074Thr	synonymous_variant	Exon 16 of 34			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.3261C>A	p.Thr1087Thr	synonymous_variant	Exon 16 of 36			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.3261C>A	p.Thr1087Thr	synonymous_variant	Exon 16 of 35			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.3261C>A	p.Thr1087Thr	synonymous_variant	Exon 16 of 36			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.3261C>A	p.Thr1087Thr	synonymous_variant	Exon 16 of 35			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.3261C>A	p.Thr1087Thr	synonymous_variant	Exon 16 of 34			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.3261C>A		non_coding_transcript_exon_variant	Exon 16 of 37	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.3261C>A		non_coding_transcript_exon_variant	Exon 16 of 34	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.3261C>A		non_coding_transcript_exon_variant	Exon 16 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*1174C>A		non_coding_transcript_exon_variant	Exon 16 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.*2708C>A		non_coding_transcript_exon_variant	Exon 15 of 34			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.3261C>A		non_coding_transcript_exon_variant	Exon 16 of 36			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.3261C>A		non_coding_transcript_exon_variant	Exon 16 of 35			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.3261C>A		non_coding_transcript_exon_variant	Exon 16 of 36			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.3261C>A		non_coding_transcript_exon_variant	Exon 16 of 36			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.3261C>A		non_coding_transcript_exon_variant	Exon 16 of 36			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.3261C>A		non_coding_transcript_exon_variant	Exon 16 of 35			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.3261C>A		non_coding_transcript_exon_variant	Exon 16 of 37			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.3261C>A		non_coding_transcript_exon_variant	Exon 16 of 36			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.3261C>A		non_coding_transcript_exon_variant	Exon 16 of 35			ENSP00000518777.1
CACNA1H	ENST00000640028.1 link	n.*1174C>A		3_prime_UTR_variant	Exon 16 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.*2708C>A		3_prime_UTR_variant	Exon 15 of 34			ENSP00000518758.1

Frequencies

GnomAD3 genomes

AF:

0.000697

AC:

106

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000909

AC:

197

AN:

216624

AF XY:

0.000934

show subpopulations

Gnomad AFR exome

AF:

0.0000812

Gnomad AMR exome

AF:

0.0000943

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00140

Gnomad NFE exome

AF:

0.00153

Gnomad OTH exome

AF:

0.00146

GnomAD4 exome

AF:

0.000935

AC:

1348

AN:

1441884

Hom.:

Cov.:

AF XY:

0.000904

AC XY:

647

AN XY:

715504

show subpopulations

African (AFR)

AF:

0.0000608

AC:

AN:

32904

American (AMR)

AF:

0.0000940

AC:

AN:

42536

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25748

East Asian (EAS)

AF:

0.00

AC:

AN:

38390

South Asian (SAS)

AF:

0.000399

AC:

AN:

82702

European-Finnish (FIN)

AF:

0.00159

AC:

AN:

50868

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5352

European-Non Finnish (NFE)

AF:

0.00104

AC:

1150

AN:

1103702

Other (OTH)

AF:

0.00131

AC:

AN:

59682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

172

259

345

431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

108

144

180

<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:

0.000696

AC:

106

AN:

152304

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41566

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00188

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00112

AC:

AN:

68028

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

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:

0.000960

Hom.:

Bravo

AF:

0.000623

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:1

Jul 25, 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

Feb 02, 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

-0.56

CADD

Benign

1.4

(source)

DANN

Benign

0.76

PhyloP100

-5.3

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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