16-1195503-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_021098.3(CACNA1H):c.483C>T(p.Phe161Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000481 in 1,600,314 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.04

Publications

7 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 16-1195503-C-T is Benign according to our data. Variant chr16-1195503-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2930993.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.04 with no splicing effect.

BS2

High AC in GnomAdExome4 at 76 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.483C>T	p.Phe161Phe	synonymous_variant	Exon 4 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.483C>T	p.Phe161Phe	synonymous_variant	Exon 4 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6 link	c.483C>T	p.Phe161Phe	synonymous_variant	Exon 4 of 34	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1 link	c.483C>T	p.Phe161Phe	synonymous_variant	Exon 4 of 34			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.483C>T	p.Phe161Phe	synonymous_variant	Exon 4 of 34	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000711450.1 link	c.483C>T	p.Phe161Phe	synonymous_variant	Exon 4 of 35			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.483C>T	p.Phe161Phe	synonymous_variant	Exon 4 of 35	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000638323.1 link	c.444C>T	p.Phe148Phe	synonymous_variant	Exon 4 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000562079.6 link	c.483C>T	p.Phe161Phe	synonymous_variant	Exon 4 of 34	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000711438.1 link	c.444C>T	p.Phe148Phe	synonymous_variant	Exon 4 of 34			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.483C>T	p.Phe161Phe	synonymous_variant	Exon 4 of 36			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.483C>T	p.Phe161Phe	synonymous_variant	Exon 4 of 35			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.483C>T	p.Phe161Phe	synonymous_variant	Exon 4 of 36			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.483C>T	p.Phe161Phe	synonymous_variant	Exon 4 of 35			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.483C>T	p.Phe161Phe	synonymous_variant	Exon 4 of 34			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.483C>T		non_coding_transcript_exon_variant	Exon 4 of 37	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.483C>T		non_coding_transcript_exon_variant	Exon 4 of 34	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.483C>T		non_coding_transcript_exon_variant	Exon 4 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.483C>T		non_coding_transcript_exon_variant	Exon 4 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.483C>T		non_coding_transcript_exon_variant	Exon 4 of 34			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.483C>T		non_coding_transcript_exon_variant	Exon 4 of 36			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.483C>T		non_coding_transcript_exon_variant	Exon 4 of 35			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.483C>T		non_coding_transcript_exon_variant	Exon 4 of 36			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.483C>T		non_coding_transcript_exon_variant	Exon 4 of 36			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.483C>T		non_coding_transcript_exon_variant	Exon 4 of 36			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.483C>T		non_coding_transcript_exon_variant	Exon 4 of 35			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.483C>T		non_coding_transcript_exon_variant	Exon 4 of 37			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.483C>T		non_coding_transcript_exon_variant	Exon 4 of 36			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.483C>T		non_coding_transcript_exon_variant	Exon 4 of 35			ENSP00000518777.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000220

AC:

AN:

227114

AF XY:

0.0000163

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:

0.0000496

Gnomad NFE exome

AF:

0.0000392

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000525

AC:

AN:

1448272

Hom.:

Cov.:

AF XY:

0.0000515

AC XY:

AN XY:

718856

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33266

American (AMR)

AF:

0.00

AC:

AN:

42782

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25866

East Asian (EAS)

AF:

0.00

AC:

AN:

39100

South Asian (SAS)

AF:

0.00

AC:

AN:

83460

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52446

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.0000633

AC:

AN:

1105714

Other (OTH)

AF:

0.000100

AC:

AN:

59922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.00000658

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41390

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Likely 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

Dec 19, 2023

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

-0.43

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

-1.0

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over