GeneBe

rs1555520987

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000711482.1(CACNA1H):​c.6373G>A​(p.Gly2125Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict 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: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CACNA1H
ENST00000711482.1 missense

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.550

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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 16-1220412-G-A is Benign according to our data. Variant chr16-1220412-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 460168.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1HNM_021098.3 linkc.6480G>A p.Leu2160Leu synonymous_variant Exon 35 of 35 ENST00000348261.11 NP_066921.2 O95180-1B3KQH9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA1HENST00000711482.1 linkc.6373G>A p.Gly2125Arg missense_variant Exon 36 of 36 ENSP00000518771.1
CACNA1HENST00000711485.1 linkc.6322G>A p.Gly2108Arg missense_variant Exon 35 of 35 ENSP00000518774.1
CACNA1HENST00000711455.1 linkc.6295G>A p.Gly2099Arg missense_variant Exon 36 of 36 ENSP00000518768.1
CACNA1HENST00000348261.11 linkc.6480G>A p.Leu2160Leu synonymous_variant Exon 35 of 35 1 NM_021098.3 ENSP00000334198.7 O95180-1
CACNA1HENST00000569107.6 linkc.6495G>A p.Leu2165Leu synonymous_variant Exon 34 of 34 1 ENSP00000454990.2 H3BNT0
CACNA1HENST00000711493.1 linkc.6465G>A p.Leu2155Leu synonymous_variant Exon 34 of 34 ENSP00000518778.1
CACNA1HENST00000565831.7 linkc.6462G>A p.Leu2154Leu synonymous_variant Exon 34 of 34 1 ENSP00000455840.1 O95180-2
CACNA1HENST00000711450.1 linkc.6462G>A p.Leu2154Leu synonymous_variant Exon 35 of 35 ENSP00000518762.1
CACNA1HENST00000564231.6 linkc.6447G>A p.Leu2149Leu synonymous_variant Exon 35 of 35 1 ENSP00000457555.2 H3BUA8
CACNA1HENST00000638323.1 linkc.6441G>A p.Leu2147Leu synonymous_variant Exon 35 of 35 5 ENSP00000492267.1 A0A1W2PR14
CACNA1HENST00000562079.6 linkc.6429G>A p.Leu2143Leu synonymous_variant Exon 34 of 34 1 ENSP00000454581.2 H3BMW6
CACNA1HENST00000711438.1 linkc.6423G>A p.Leu2141Leu synonymous_variant Exon 34 of 34 ENSP00000518754.1
CACNA1HENST00000637236.3 linkn.*2399G>A non_coding_transcript_exon_variant Exon 34 of 34 5 ENSP00000492650.2 A0A1W2PS38
CACNA1HENST00000639478.1 linkn.*1528G>A non_coding_transcript_exon_variant Exon 35 of 35 5 ENSP00000491945.1 A0A1W2PQW2
CACNA1HENST00000640028.1 linkn.*4298G>A non_coding_transcript_exon_variant Exon 35 of 35 5 ENSP00000491488.1 A0A1W2PQ19
CACNA1HENST00000711442.1 linkn.*5924G>A non_coding_transcript_exon_variant Exon 33 of 34 ENSP00000518758.1
CACNA1HENST00000711448.1 linkn.*1421G>A non_coding_transcript_exon_variant Exon 36 of 36 ENSP00000518760.1
CACNA1HENST00000711449.1 linkn.*1339G>A non_coding_transcript_exon_variant Exon 35 of 35 ENSP00000518761.1
CACNA1HENST00000711451.1 linkn.*2059G>A non_coding_transcript_exon_variant Exon 36 of 36 ENSP00000518763.1
CACNA1HENST00000711452.1 linkn.*1147G>A non_coding_transcript_exon_variant Exon 36 of 36 ENSP00000518764.1
CACNA1HENST00000711453.1 linkn.*1114G>A non_coding_transcript_exon_variant Exon 36 of 36 ENSP00000518765.1
CACNA1HENST00000711484.1 linkn.*394G>A non_coding_transcript_exon_variant Exon 34 of 35 ENSP00000518773.1
CACNA1HENST00000711486.1 linkn.6480G>A non_coding_transcript_exon_variant Exon 35 of 37 ENSP00000518775.1
CACNA1HENST00000711487.1 linkn.6447G>A non_coding_transcript_exon_variant Exon 35 of 36 ENSP00000518776.1
CACNA1HENST00000711488.1 linkn.*1596G>A non_coding_transcript_exon_variant Exon 35 of 35 ENSP00000518777.1
CACNA1HENST00000711483.1 linkc.*394G>A 3_prime_UTR_variant Exon 35 of 35 ENSP00000518772.1
CACNA1HENST00000711456.1 linkc.*394G>A 3_prime_UTR_variant Exon 34 of 34 ENSP00000518769.1
CACNA1HENST00000637236.3 linkn.*2399G>A 3_prime_UTR_variant Exon 34 of 34 5 ENSP00000492650.2 A0A1W2PS38
CACNA1HENST00000639478.1 linkn.*1528G>A 3_prime_UTR_variant Exon 35 of 35 5 ENSP00000491945.1 A0A1W2PQW2
CACNA1HENST00000640028.1 linkn.*4298G>A 3_prime_UTR_variant Exon 35 of 35 5 ENSP00000491488.1 A0A1W2PQ19
CACNA1HENST00000711442.1 linkn.*5924G>A 3_prime_UTR_variant Exon 33 of 34 ENSP00000518758.1
CACNA1HENST00000711448.1 linkn.*1421G>A 3_prime_UTR_variant Exon 36 of 36 ENSP00000518760.1
CACNA1HENST00000711449.1 linkn.*1339G>A 3_prime_UTR_variant Exon 35 of 35 ENSP00000518761.1
CACNA1HENST00000711451.1 linkn.*2059G>A 3_prime_UTR_variant Exon 36 of 36 ENSP00000518763.1
CACNA1HENST00000711452.1 linkn.*1147G>A 3_prime_UTR_variant Exon 36 of 36 ENSP00000518764.1
CACNA1HENST00000711453.1 linkn.*1114G>A 3_prime_UTR_variant Exon 36 of 36 ENSP00000518765.1
CACNA1HENST00000711484.1 linkn.*394G>A 3_prime_UTR_variant Exon 34 of 35 ENSP00000518773.1
CACNA1HENST00000711488.1 linkn.*1596G>A 3_prime_UTR_variant Exon 35 of 35 ENSP00000518777.1
CACNA1HENST00000621827.2 linkn.6121+359G>A intron_variant Intron 35 of 36 6 ENSP00000518766.1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152226
Hom.:
0
Cov.:
33
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
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1377516
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
680064
African (AFR)
AF:
0.00
AC:
0
AN:
29520
American (AMR)
AF:
0.00
AC:
0
AN:
29648
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
20432
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38020
South Asian (SAS)
AF:
0.00
AC:
0
AN:
72456
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
45932
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5342
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1079610
Other (OTH)
AF:
0.00
AC:
0
AN:
56556
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152226
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74372
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41472
American (AMR)
AF:
0.00
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5190
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68018
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0
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
Jun 21, 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
-0.81
CADD
Benign
0.34
DANN
Benign
0.75
PhyloP100
-0.55

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

Other links and lift over

dbSNP: rs1555520987; hg19: chr16-1270412; API