rs369924266

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_021098.3(CACNA1H):​c.3060G>A​(p.Ala1020Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000565 in 1,612,848 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00059 ( 13 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.45

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: Benign. The variant received -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 16-1207427-G-A is Benign according to our data. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-1207427-G-A is described in CliVar as Benign. Clinvar id is 529659.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.45 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000361 (55/152256) while in subpopulation SAS AF = 0.00995 (48/4824). AF 95% confidence interval is 0.00771. There are 0 homozygotes in GnomAd4. There are 42 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
BS2
High AC in GnomAd4 at 55 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1HNM_021098.3 linkc.3060G>A p.Ala1020Ala synonymous_variant Exon 14 of 35 ENST00000348261.11 NP_066921.2 O95180-1B3KQH9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA1HENST00000348261.11 linkc.3060G>A p.Ala1020Ala synonymous_variant Exon 14 of 35 1 NM_021098.3 ENSP00000334198.7 O95180-1
CACNA1HENST00000569107.6 linkc.3060G>A p.Ala1020Ala synonymous_variant Exon 14 of 34 1 ENSP00000454990.2 H3BNT0
CACNA1HENST00000711493.1 linkc.3060G>A p.Ala1020Ala synonymous_variant Exon 14 of 34 ENSP00000518778.1
CACNA1HENST00000565831.7 linkc.3060G>A p.Ala1020Ala synonymous_variant Exon 14 of 34 1 ENSP00000455840.1 O95180-2
CACNA1HENST00000711450.1 linkc.3060G>A p.Ala1020Ala synonymous_variant Exon 14 of 35 ENSP00000518762.1
CACNA1HENST00000564231.6 linkc.3060G>A p.Ala1020Ala synonymous_variant Exon 14 of 35 1 ENSP00000457555.2 H3BUA8
CACNA1HENST00000638323.1 linkc.3021G>A p.Ala1007Ala synonymous_variant Exon 14 of 35 5 ENSP00000492267.1 A0A1W2PR14
CACNA1HENST00000562079.6 linkc.3060G>A p.Ala1020Ala synonymous_variant Exon 14 of 34 1 ENSP00000454581.2 H3BMW6
CACNA1HENST00000711438.1 linkc.3021G>A p.Ala1007Ala synonymous_variant Exon 14 of 34 ENSP00000518754.1
CACNA1HENST00000711482.1 linkc.3060G>A p.Ala1020Ala synonymous_variant Exon 14 of 36 ENSP00000518771.1
CACNA1HENST00000711485.1 linkc.3060G>A p.Ala1020Ala synonymous_variant Exon 14 of 35 ENSP00000518774.1
CACNA1HENST00000711455.1 linkc.3060G>A p.Ala1020Ala synonymous_variant Exon 14 of 36 ENSP00000518768.1
CACNA1HENST00000711483.1 linkc.3060G>A p.Ala1020Ala synonymous_variant Exon 14 of 35 ENSP00000518772.1
CACNA1HENST00000711456.1 linkc.3060G>A p.Ala1020Ala synonymous_variant Exon 14 of 34 ENSP00000518769.1
CACNA1HENST00000621827.2 linkn.3060G>A non_coding_transcript_exon_variant Exon 14 of 37 6 ENSP00000518766.1
CACNA1HENST00000637236.3 linkn.3060G>A non_coding_transcript_exon_variant Exon 14 of 34 5 ENSP00000492650.2 A0A1W2PS38
CACNA1HENST00000639478.1 linkn.3060G>A non_coding_transcript_exon_variant Exon 14 of 35 5 ENSP00000491945.1 A0A1W2PQW2
CACNA1HENST00000640028.1 linkn.*973G>A non_coding_transcript_exon_variant Exon 14 of 35 5 ENSP00000491488.1 A0A1W2PQ19
CACNA1HENST00000711442.1 linkn.*2507G>A non_coding_transcript_exon_variant Exon 13 of 34 ENSP00000518758.1
CACNA1HENST00000711448.1 linkn.3060G>A non_coding_transcript_exon_variant Exon 14 of 36 ENSP00000518760.1
CACNA1HENST00000711449.1 linkn.3060G>A non_coding_transcript_exon_variant Exon 14 of 35 ENSP00000518761.1
CACNA1HENST00000711451.1 linkn.3060G>A non_coding_transcript_exon_variant Exon 14 of 36 ENSP00000518763.1
CACNA1HENST00000711452.1 linkn.3060G>A non_coding_transcript_exon_variant Exon 14 of 36 ENSP00000518764.1
CACNA1HENST00000711453.1 linkn.3060G>A non_coding_transcript_exon_variant Exon 14 of 36 ENSP00000518765.1
CACNA1HENST00000711484.1 linkn.3060G>A non_coding_transcript_exon_variant Exon 14 of 35 ENSP00000518773.1
CACNA1HENST00000711486.1 linkn.3060G>A non_coding_transcript_exon_variant Exon 14 of 37 ENSP00000518775.1
CACNA1HENST00000711487.1 linkn.3060G>A non_coding_transcript_exon_variant Exon 14 of 36 ENSP00000518776.1
CACNA1HENST00000711488.1 linkn.3060G>A non_coding_transcript_exon_variant Exon 14 of 35 ENSP00000518777.1
CACNA1HENST00000640028.1 linkn.*973G>A 3_prime_UTR_variant Exon 14 of 35 5 ENSP00000491488.1 A0A1W2PQ19
CACNA1HENST00000711442.1 linkn.*2507G>A 3_prime_UTR_variant Exon 13 of 34 ENSP00000518758.1

Frequencies

GnomAD3 genomes
AF:
0.000362
AC:
55
AN:
152138
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00994
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00106
AC:
263
AN:
246968
AF XY:
0.00136
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:
0.0000628
Gnomad OTH exome
AF:
0.000498
GnomAD4 exome
AF:
0.000587
AC:
857
AN:
1460592
Hom.:
13
Cov.:
33
AF XY:
0.000827
AC XY:
601
AN XY:
726550
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33474
American (AMR)
AF:
0.00
AC:
0
AN:
44684
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26128
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39694
South Asian (SAS)
AF:
0.00817
AC:
704
AN:
86194
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52554
Middle Eastern (MID)
AF:
0.000521
AC:
3
AN:
5762
European-Non Finnish (NFE)
AF:
0.0000846
AC:
94
AN:
1111746
Other (OTH)
AF:
0.000911
AC:
55
AN:
60356
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
47
95
142
190
237
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20
40
60
80
100
<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:
0.000361
AC:
55
AN:
152256
Hom.:
0
Cov.:
30
AF XY:
0.000564
AC XY:
42
AN XY:
74446
show subpopulations
African (AFR)
AF:
0.0000963
AC:
4
AN:
41558
American (AMR)
AF:
0.00
AC:
0
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5170
South Asian (SAS)
AF:
0.00995
AC:
48
AN:
4824
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000441
AC:
3
AN:
68010
Other (OTH)
AF:
0.00
AC:
0
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.490
Heterozygous variant carriers
0
3
5
8
10
13
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:
0.000151
Hom.:
0
Bravo
AF:
0.0000869
Asia WGS
AF:
0.00375
AC:
13
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.00

ClinVar

Significance: 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
Jan 22, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: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
-0.73
CADD
Benign
1.2
DANN
Benign
0.86
PhyloP100
-2.4
Mutation Taster
=96/4
polymorphism

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: rs369924266; hg19: chr16-1257427; COSMIC: COSV61988351; COSMIC: COSV61988351; API