chr16-1207298-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_021098.3(CACNA1H):c.2931C>T(p.Asn977Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000429 in 1,610,150 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.367

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:

ENSG00000261294 (HGNC:):

ENSG00000261294 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=-0.38).

BP6

Variant 16-1207298-C-T is Benign according to our data. Variant chr16-1207298-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 529644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.367 with no splicing effect.

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.2931C>T	p.Asn977Asn	synonymous_variant	Exon 14 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.2931C>T	p.Asn977Asn	synonymous_variant	Exon 14 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6 link	c.2931C>T	p.Asn977Asn	synonymous_variant	Exon 14 of 34	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1 link	c.2931C>T	p.Asn977Asn	synonymous_variant	Exon 14 of 34			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.2931C>T	p.Asn977Asn	synonymous_variant	Exon 14 of 34	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000711450.1 link	c.2931C>T	p.Asn977Asn	synonymous_variant	Exon 14 of 35			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.2931C>T	p.Asn977Asn	synonymous_variant	Exon 14 of 35	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000638323.1 link	c.2892C>T	p.Asn964Asn	synonymous_variant	Exon 14 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000562079.6 link	c.2931C>T	p.Asn977Asn	synonymous_variant	Exon 14 of 34	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000711438.1 link	c.2892C>T	p.Asn964Asn	synonymous_variant	Exon 14 of 34			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.2931C>T	p.Asn977Asn	synonymous_variant	Exon 14 of 36			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.2931C>T	p.Asn977Asn	synonymous_variant	Exon 14 of 35			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.2931C>T	p.Asn977Asn	synonymous_variant	Exon 14 of 36			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.2931C>T	p.Asn977Asn	synonymous_variant	Exon 14 of 35			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.2931C>T	p.Asn977Asn	synonymous_variant	Exon 14 of 34			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.2931C>T		non_coding_transcript_exon_variant	Exon 14 of 37	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.2931C>T		non_coding_transcript_exon_variant	Exon 14 of 34	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.2931C>T		non_coding_transcript_exon_variant	Exon 14 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*844C>T		non_coding_transcript_exon_variant	Exon 14 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.*2378C>T		non_coding_transcript_exon_variant	Exon 13 of 34			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.2931C>T		non_coding_transcript_exon_variant	Exon 14 of 36			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.2931C>T		non_coding_transcript_exon_variant	Exon 14 of 35			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.2931C>T		non_coding_transcript_exon_variant	Exon 14 of 36			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.2931C>T		non_coding_transcript_exon_variant	Exon 14 of 36			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.2931C>T		non_coding_transcript_exon_variant	Exon 14 of 36			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.2931C>T		non_coding_transcript_exon_variant	Exon 14 of 35			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.2931C>T		non_coding_transcript_exon_variant	Exon 14 of 37			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.2931C>T		non_coding_transcript_exon_variant	Exon 14 of 36			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.2931C>T		non_coding_transcript_exon_variant	Exon 14 of 35			ENSP00000518777.1
CACNA1H	ENST00000640028.1 link	n.*844C>T		3_prime_UTR_variant	Exon 14 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.*2378C>T		3_prime_UTR_variant	Exon 13 of 34			ENSP00000518758.1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000331

AC:

AN:

241824

AF XY:

0.0000228

show subpopulations

Gnomad AFR exome

AF:

0.000205

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:

0.0000368

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1458110

Hom.:

Cov.:

AF XY:

0.0000345

AC XY:

AN XY:

725094

show subpopulations

African (AFR)

AF:

0.000419

AC:

AN:

33416

American (AMR)

AF:

0.0000226

AC:

AN:

44288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26030

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39616

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000279

AC:

AN:

1110404

Other (OTH)

AF:

0.0000498

AC:

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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

AF:

0.000105

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.000290

AC:

AN:

41410

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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:

0.0000773

Hom.:

Bravo

AF:

0.000102

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

Dec 23, 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 05, 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

-0.38

CADD

Benign

4.4

(source)

DANN

Benign

0.93

PhyloP100

-0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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