rs372041705

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_021098.3(CACNA1H):c.366C>G(p.Pro122Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,610,716 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 0.000013 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.564

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 16-1195038-C-G is Benign according to our data. Variant chr16-1195038-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 460095.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.564 with no splicing effect.

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 3 of 35	ENST00000348261.11	NP_066921.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CACNA1H	ENST00000348261.11 link	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 3 of 35	1	NM_021098.3	ENSP00000334198.7
CACNA1H	ENST00000569107.6 link	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 3 of 34	1		ENSP00000454990.2
CACNA1H	ENST00000711493.1 link	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 3 of 34			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 3 of 34	1		ENSP00000455840.1
CACNA1H	ENST00000711450.1 link	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 3 of 35			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 3 of 35	1		ENSP00000457555.2
CACNA1H	ENST00000638323.1 link	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 3 of 35	5		ENSP00000492267.1
CACNA1H	ENST00000562079.6 link	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 3 of 34	1		ENSP00000454581.2
CACNA1H	ENST00000711438.1 link	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 3 of 34			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 3 of 36			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 3 of 35			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 3 of 36			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 3 of 35			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.366C>G	p.Pro122Pro	synonymous_variant	Exon 3 of 34			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.366C>G		non_coding_transcript_exon_variant	Exon 3 of 37	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.366C>G		non_coding_transcript_exon_variant	Exon 3 of 34	5		ENSP00000492650.2
CACNA1H	ENST00000639478.1 link	n.366C>G		non_coding_transcript_exon_variant	Exon 3 of 35	5		ENSP00000491945.1
CACNA1H	ENST00000640028.1 link	n.366C>G		non_coding_transcript_exon_variant	Exon 3 of 35	5		ENSP00000491488.1
CACNA1H	ENST00000711442.1 link	n.366C>G		non_coding_transcript_exon_variant	Exon 3 of 34			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.366C>G		non_coding_transcript_exon_variant	Exon 3 of 36			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.366C>G		non_coding_transcript_exon_variant	Exon 3 of 35			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.366C>G		non_coding_transcript_exon_variant	Exon 3 of 36			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.366C>G		non_coding_transcript_exon_variant	Exon 3 of 36			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.366C>G		non_coding_transcript_exon_variant	Exon 3 of 36			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.366C>G		non_coding_transcript_exon_variant	Exon 3 of 35			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.366C>G		non_coding_transcript_exon_variant	Exon 3 of 37			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.366C>G		non_coding_transcript_exon_variant	Exon 3 of 36			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.366C>G		non_coding_transcript_exon_variant	Exon 3 of 35			ENSP00000518777.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151568

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00000806

AC:

AN:

248256

AF XY:

0.0000148

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1459148

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725712

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26096

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1110738

Other (OTH)

AF:

0.00

AC:

AN:

60262

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

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151568

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73982

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41250

American (AMR)

AF:

0.00

AC:

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10464

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67924

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

Feb 10, 2022

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

-0.60

CADD

Benign

8.7

(source)

DANN

Benign

0.83

PhyloP100

0.56

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over