GeneBe

rs8044363

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_021098.3(CACNA1H):​c.1107T>A​(p.Ile369Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I369I) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.69
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]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP7
Synonymous conserved (PhyloP=-2.69 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1HNM_021098.3 linkc.1107T>A p.Ile369Ile synonymous_variant Exon 7 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.1107T>A p.Ile369Ile synonymous_variant Exon 7 of 35 1 NM_021098.3 ENSP00000334198.7 O95180-1
CACNA1HENST00000569107.6 linkc.1107T>A p.Ile369Ile synonymous_variant Exon 7 of 34 1 ENSP00000454990.2 H3BNT0
CACNA1HENST00000711493.1 linkc.1107T>A p.Ile369Ile synonymous_variant Exon 7 of 34 ENSP00000518778.1
CACNA1HENST00000565831.7 linkc.1107T>A p.Ile369Ile synonymous_variant Exon 7 of 34 1 ENSP00000455840.1 O95180-2
CACNA1HENST00000711450.1 linkc.1107T>A p.Ile369Ile synonymous_variant Exon 7 of 35 ENSP00000518762.1
CACNA1HENST00000564231.6 linkc.1107T>A p.Ile369Ile synonymous_variant Exon 7 of 35 1 ENSP00000457555.2 H3BUA8
CACNA1HENST00000638323.1 linkc.1068T>A p.Ile356Ile synonymous_variant Exon 7 of 35 5 ENSP00000492267.1 A0A1W2PR14
CACNA1HENST00000562079.6 linkc.1107T>A p.Ile369Ile synonymous_variant Exon 7 of 34 1 ENSP00000454581.2 H3BMW6
CACNA1HENST00000711438.1 linkc.1068T>A p.Ile356Ile synonymous_variant Exon 7 of 34 ENSP00000518754.1
CACNA1HENST00000711482.1 linkc.1107T>A p.Ile369Ile synonymous_variant Exon 7 of 36 ENSP00000518771.1
CACNA1HENST00000711485.1 linkc.1107T>A p.Ile369Ile synonymous_variant Exon 7 of 35 ENSP00000518774.1
CACNA1HENST00000711455.1 linkc.1107T>A p.Ile369Ile synonymous_variant Exon 7 of 36 ENSP00000518768.1
CACNA1HENST00000711483.1 linkc.1107T>A p.Ile369Ile synonymous_variant Exon 7 of 35 ENSP00000518772.1
CACNA1HENST00000711456.1 linkc.1107T>A p.Ile369Ile synonymous_variant Exon 7 of 34 ENSP00000518769.1
CACNA1HENST00000621827.2 linkn.1107T>A non_coding_transcript_exon_variant Exon 7 of 37 6 ENSP00000518766.1
CACNA1HENST00000637236.3 linkn.1107T>A non_coding_transcript_exon_variant Exon 7 of 34 5 ENSP00000492650.2 A0A1W2PS38
CACNA1HENST00000639478.1 linkn.1107T>A non_coding_transcript_exon_variant Exon 7 of 35 5 ENSP00000491945.1 A0A1W2PQW2
CACNA1HENST00000640028.1 linkn.1107T>A non_coding_transcript_exon_variant Exon 7 of 35 5 ENSP00000491488.1 A0A1W2PQ19
CACNA1HENST00000711442.1 linkn.*554T>A non_coding_transcript_exon_variant Exon 6 of 34 ENSP00000518758.1
CACNA1HENST00000711448.1 linkn.1107T>A non_coding_transcript_exon_variant Exon 7 of 36 ENSP00000518760.1
CACNA1HENST00000711449.1 linkn.1107T>A non_coding_transcript_exon_variant Exon 7 of 35 ENSP00000518761.1
CACNA1HENST00000711451.1 linkn.1107T>A non_coding_transcript_exon_variant Exon 7 of 36 ENSP00000518763.1
CACNA1HENST00000711452.1 linkn.1107T>A non_coding_transcript_exon_variant Exon 7 of 36 ENSP00000518764.1
CACNA1HENST00000711453.1 linkn.1107T>A non_coding_transcript_exon_variant Exon 7 of 36 ENSP00000518765.1
CACNA1HENST00000711484.1 linkn.1107T>A non_coding_transcript_exon_variant Exon 7 of 35 ENSP00000518773.1
CACNA1HENST00000711486.1 linkn.1107T>A non_coding_transcript_exon_variant Exon 7 of 37 ENSP00000518775.1
CACNA1HENST00000711487.1 linkn.1107T>A non_coding_transcript_exon_variant Exon 7 of 36 ENSP00000518776.1
CACNA1HENST00000711488.1 linkn.1107T>A non_coding_transcript_exon_variant Exon 7 of 35 ENSP00000518777.1
CACNA1HENST00000711442.1 linkn.*554T>A 3_prime_UTR_variant Exon 6 of 34 ENSP00000518758.1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151970
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: AS_VQSR
AF:
6.85e-7
AC:
1
AN:
1459540
Hom.:
0
Cov.:
46
AF XY:
0.00000138
AC XY:
1
AN XY:
726092
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33470
American (AMR)
AF:
0.00
AC:
0
AN:
44686
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26100
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39690
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86242
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51656
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
9.00e-7
AC:
1
AN:
1111608
Other (OTH)
AF:
0.00
AC:
0
AN:
60324
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
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

Exome 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
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151970
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74190
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41352
American (AMR)
AF:
0.00
AC:
0
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5180
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10586
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67966
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
7728

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
1.6
DANN
Benign
0.86
PhyloP100
-2.7

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: rs8044363; hg19: chr16-1250559; API