rs1182772693

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.5145C>T(p.Arg1715Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,611,472 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: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0870

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 16-1215347-C-T is Benign according to our data. Variant chr16-1215347-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 460138.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.087 with no splicing effect.

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1H	NM_021098.3 link	c.5145C>T	p.Arg1715Arg	synonymous_variant	Exon 29 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.5145C>T	p.Arg1715Arg	synonymous_variant	Exon 29 of 35	1	NM_021098.3	ENSP00000334198.7	O95180-1
CACNA1H	ENST00000569107.6 link	c.5160C>T	p.Arg1720Arg	synonymous_variant	Exon 28 of 34	1		ENSP00000454990.2	H3BNT0
CACNA1H	ENST00000711493.1 link	c.5163C>T	p.Arg1721Arg	synonymous_variant	Exon 28 of 34			ENSP00000518778.1
CACNA1H	ENST00000565831.7 link	c.5127C>T	p.Arg1709Arg	synonymous_variant	Exon 28 of 34	1		ENSP00000455840.1	O95180-2
CACNA1H	ENST00000711450.1 link	c.5160C>T	p.Arg1720Arg	synonymous_variant	Exon 29 of 35			ENSP00000518762.1
CACNA1H	ENST00000564231.6 link	c.5145C>T	p.Arg1715Arg	synonymous_variant	Exon 29 of 35	1		ENSP00000457555.2	H3BUA8
CACNA1H	ENST00000638323.1 link	c.5106C>T	p.Arg1702Arg	synonymous_variant	Exon 29 of 35	5		ENSP00000492267.1	A0A1W2PR14
CACNA1H	ENST00000562079.6 link	c.5127C>T	p.Arg1709Arg	synonymous_variant	Exon 28 of 34	1		ENSP00000454581.2	H3BMW6
CACNA1H	ENST00000711438.1 link	c.5088C>T	p.Arg1696Arg	synonymous_variant	Exon 28 of 34			ENSP00000518754.1
CACNA1H	ENST00000711482.1 link	c.5145C>T	p.Arg1715Arg	synonymous_variant	Exon 29 of 36			ENSP00000518771.1
CACNA1H	ENST00000711485.1 link	c.5127C>T	p.Arg1709Arg	synonymous_variant	Exon 28 of 35			ENSP00000518774.1
CACNA1H	ENST00000711455.1 link	c.5145C>T	p.Arg1715Arg	synonymous_variant	Exon 29 of 36			ENSP00000518768.1
CACNA1H	ENST00000711483.1 link	c.5145C>T	p.Arg1715Arg	synonymous_variant	Exon 29 of 35			ENSP00000518772.1
CACNA1H	ENST00000711456.1 link	c.5145C>T	p.Arg1715Arg	synonymous_variant	Exon 29 of 34			ENSP00000518769.1
CACNA1H	ENST00000621827.2 link	n.5145C>T		non_coding_transcript_exon_variant	Exon 29 of 37	6		ENSP00000518766.1
CACNA1H	ENST00000637236.3 link	n.*1097C>T		non_coding_transcript_exon_variant	Exon 28 of 34	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.*226C>T		non_coding_transcript_exon_variant	Exon 29 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*2996C>T		non_coding_transcript_exon_variant	Exon 29 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.*4589C>T		non_coding_transcript_exon_variant	Exon 27 of 34			ENSP00000518758.1
CACNA1H	ENST00000711448.1 link	n.5127C>T		non_coding_transcript_exon_variant	Exon 28 of 36			ENSP00000518760.1
CACNA1H	ENST00000711449.1 link	n.5127C>T		non_coding_transcript_exon_variant	Exon 28 of 35			ENSP00000518761.1
CACNA1H	ENST00000711451.1 link	n.*146C>T		non_coding_transcript_exon_variant	Exon 29 of 36			ENSP00000518763.1
CACNA1H	ENST00000711452.1 link	n.5145C>T		non_coding_transcript_exon_variant	Exon 29 of 36			ENSP00000518764.1
CACNA1H	ENST00000711453.1 link	n.5145C>T		non_coding_transcript_exon_variant	Exon 29 of 36			ENSP00000518765.1
CACNA1H	ENST00000711484.1 link	n.5127C>T		non_coding_transcript_exon_variant	Exon 28 of 35			ENSP00000518773.1
CACNA1H	ENST00000711486.1 link	n.5145C>T		non_coding_transcript_exon_variant	Exon 29 of 37			ENSP00000518775.1
CACNA1H	ENST00000711487.1 link	n.5145C>T		non_coding_transcript_exon_variant	Exon 29 of 36			ENSP00000518776.1
CACNA1H	ENST00000711488.1 link	n.*146C>T		non_coding_transcript_exon_variant	Exon 28 of 35			ENSP00000518777.1
CACNA1H	ENST00000637236.3 link	n.*1097C>T		3_prime_UTR_variant	Exon 28 of 34	5		ENSP00000492650.2	A0A1W2PS38
CACNA1H	ENST00000639478.1 link	n.*226C>T		3_prime_UTR_variant	Exon 29 of 35	5		ENSP00000491945.1	A0A1W2PQW2
CACNA1H	ENST00000640028.1 link	n.*2996C>T		3_prime_UTR_variant	Exon 29 of 35	5		ENSP00000491488.1	A0A1W2PQ19
CACNA1H	ENST00000711442.1 link	n.*4589C>T		3_prime_UTR_variant	Exon 27 of 34			ENSP00000518758.1
CACNA1H	ENST00000711451.1 link	n.*146C>T		3_prime_UTR_variant	Exon 29 of 36			ENSP00000518763.1
CACNA1H	ENST00000711488.1 link	n.*146C>T		3_prime_UTR_variant	Exon 28 of 35			ENSP00000518777.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151960

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1459512

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

725952

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.00

AC:

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

86034

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000900

AC:

AN:

1111308

Other (OTH)

AF:

0.00

AC:

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.0000132

AC:

AN:

151960

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74246

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67962

Other (OTH)

AF:

0.00

AC:

AN:

2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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:

0.0000540

Hom.:

Bravo

AF:

0.00000378

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

Apr 17, 2017

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

-0.44

CADD

Benign

4.0

(source)

DANN

Benign

0.96

PhyloP100

-0.087

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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over