16-1206260-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_021098.3(CACNA1H):c.2760G>T(p.Thr920Thr) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,569,624 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. T920T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.68

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 16-1206260-G-T is Benign according to our data. Variant chr16-1206260-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 529636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.2760G>T	p.Thr920Thr	synonymous_variant	Exon 12 of 35	ENST00000348261.11	NP_066921.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CACNA1H	ENST00000348261.11 link	c.2760G>T	p.Thr920Thr	synonymous_variant	Exon 12 of 35	1	NM_021098.3	ENSP00000334198.7
CACNA1H	ENST00000569107.6 link	c.2760G>T	p.Thr920Thr	synonymous_variant	Exon 12 of 34	1		ENSP00000454990.2
CACNA1H	ENST00000711493.1 link	c.2760G>T	p.Thr920Thr	synonymous_variant	Exon 12 of 34			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.2760G>T	p.Thr920Thr	synonymous_variant	Exon 12 of 34	1		ENSP00000455840.1
CACNA1H	ENST00000711450.1 link	c.2760G>T	p.Thr920Thr	synonymous_variant	Exon 12 of 35			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.2760G>T	p.Thr920Thr	synonymous_variant	Exon 12 of 35	1		ENSP00000457555.2
CACNA1H	ENST00000638323.1 link	c.2721G>T	p.Thr907Thr	synonymous_variant	Exon 12 of 35	5		ENSP00000492267.1
CACNA1H	ENST00000562079.6 link	c.2760G>T	p.Thr920Thr	synonymous_variant	Exon 12 of 34	1		ENSP00000454581.2
CACNA1H	ENST00000711438.1 link	c.2721G>T	p.Thr907Thr	synonymous_variant	Exon 12 of 34			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.2760G>T	p.Thr920Thr	synonymous_variant	Exon 12 of 36			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.2760G>T	p.Thr920Thr	synonymous_variant	Exon 12 of 35			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.2760G>T	p.Thr920Thr	synonymous_variant	Exon 12 of 36			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.2760G>T	p.Thr920Thr	synonymous_variant	Exon 12 of 35			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.2760G>T	p.Thr920Thr	synonymous_variant	Exon 12 of 34			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.2760G>T		non_coding_transcript_exon_variant	Exon 12 of 37	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.2760G>T		non_coding_transcript_exon_variant	Exon 12 of 34	5		ENSP00000492650.2
CACNA1H	ENST00000639478.1 link	n.2760G>T		non_coding_transcript_exon_variant	Exon 12 of 35	5		ENSP00000491945.1
CACNA1H	ENST00000640028.1 link	n.*673G>T		non_coding_transcript_exon_variant	Exon 12 of 35	5		ENSP00000491488.1
CACNA1H	ENST00000711442.1 link	n.*2207G>T		non_coding_transcript_exon_variant	Exon 11 of 34			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.2760G>T		non_coding_transcript_exon_variant	Exon 12 of 36			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.2760G>T		non_coding_transcript_exon_variant	Exon 12 of 35			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.2760G>T		non_coding_transcript_exon_variant	Exon 12 of 36			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.2760G>T		non_coding_transcript_exon_variant	Exon 12 of 36			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.2760G>T		non_coding_transcript_exon_variant	Exon 12 of 36			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.2760G>T		non_coding_transcript_exon_variant	Exon 12 of 35			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.2760G>T		non_coding_transcript_exon_variant	Exon 12 of 37			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.2760G>T		non_coding_transcript_exon_variant	Exon 12 of 36			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.2760G>T		non_coding_transcript_exon_variant	Exon 12 of 35			ENSP00000518777.1
CACNA1H	ENST00000640028.1 link	n.*673G>T		3_prime_UTR_variant	Exon 12 of 35	5		ENSP00000491488.1
CACNA1H	ENST00000711442.1 link	n.*2207G>T		3_prime_UTR_variant	Exon 11 of 34			ENSP00000518758.1

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000382

AC:

AN:

183220

AF XY:

0.0000509

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000905

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000138

AC:

195

AN:

1417384

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

114

AN XY:

700972

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32262

American (AMR)

AF:

0.00

AC:

AN:

38862

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25404

East Asian (EAS)

AF:

0.00

AC:

AN:

37296

South Asian (SAS)

AF:

0.00

AC:

AN:

80340

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49700

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4342

European-Non Finnish (NFE)

AF:

0.000174

AC:

190

AN:

1090484

Other (OTH)

AF:

0.0000852

AC:

AN:

58694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.0000525

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41462

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

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

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:

0.0000501

Hom.:

Bravo

AF:

0.0000529

ClinVar

Significance: 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

Jan 11, 2024

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

Oct 31, 2024

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

-0.35

CADD

Benign

4.8

(source)

DANN

Benign

0.88

PhyloP100

7.7

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

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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