GeneBe

rs1427937474

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.2175T>C​(p.Arg725Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,992 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. R725R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.73

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 -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP7
Synonymous conserved (PhyloP=-2.73 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1HNM_021098.3 linkc.2175T>C p.Arg725Arg synonymous_variant Exon 10 of 35 ENST00000348261.11 NP_066921.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA1HENST00000348261.11 linkc.2175T>C p.Arg725Arg synonymous_variant Exon 10 of 35 1 NM_021098.3 ENSP00000334198.7
CACNA1HENST00000569107.6 linkc.2175T>C p.Arg725Arg synonymous_variant Exon 10 of 34 1 ENSP00000454990.2
CACNA1HENST00000711493.1 linkc.2175T>C p.Arg725Arg synonymous_variant Exon 10 of 34 ENSP00000518778.1
CACNA1HENST00000565831.7 linkc.2175T>C p.Arg725Arg synonymous_variant Exon 10 of 34 1 ENSP00000455840.1
CACNA1HENST00000711450.1 linkc.2175T>C p.Arg725Arg synonymous_variant Exon 10 of 35 ENSP00000518762.1
CACNA1HENST00000564231.6 linkc.2175T>C p.Arg725Arg synonymous_variant Exon 10 of 35 1 ENSP00000457555.2
CACNA1HENST00000638323.1 linkc.2136T>C p.Arg712Arg synonymous_variant Exon 10 of 35 5 ENSP00000492267.1
CACNA1HENST00000562079.6 linkc.2175T>C p.Arg725Arg synonymous_variant Exon 10 of 34 1 ENSP00000454581.2
CACNA1HENST00000711438.1 linkc.2136T>C p.Arg712Arg synonymous_variant Exon 10 of 34 ENSP00000518754.1
CACNA1HENST00000711482.1 linkc.2175T>C p.Arg725Arg synonymous_variant Exon 10 of 36 ENSP00000518771.1
CACNA1HENST00000711485.1 linkc.2175T>C p.Arg725Arg synonymous_variant Exon 10 of 35 ENSP00000518774.1
CACNA1HENST00000711455.1 linkc.2175T>C p.Arg725Arg synonymous_variant Exon 10 of 36 ENSP00000518768.1
CACNA1HENST00000711483.1 linkc.2175T>C p.Arg725Arg synonymous_variant Exon 10 of 35 ENSP00000518772.1
CACNA1HENST00000711456.1 linkc.2175T>C p.Arg725Arg synonymous_variant Exon 10 of 34 ENSP00000518769.1
CACNA1HENST00000621827.2 linkn.2175T>C non_coding_transcript_exon_variant Exon 10 of 37 6 ENSP00000518766.1
CACNA1HENST00000637236.3 linkn.2175T>C non_coding_transcript_exon_variant Exon 10 of 34 5 ENSP00000492650.2
CACNA1HENST00000639478.1 linkn.2175T>C non_coding_transcript_exon_variant Exon 10 of 35 5 ENSP00000491945.1
CACNA1HENST00000640028.1 linkn.*88T>C non_coding_transcript_exon_variant Exon 10 of 35 5 ENSP00000491488.1
CACNA1HENST00000711442.1 linkn.*1622T>C non_coding_transcript_exon_variant Exon 9 of 34 ENSP00000518758.1
CACNA1HENST00000711448.1 linkn.2175T>C non_coding_transcript_exon_variant Exon 10 of 36 ENSP00000518760.1
CACNA1HENST00000711449.1 linkn.2175T>C non_coding_transcript_exon_variant Exon 10 of 35 ENSP00000518761.1
CACNA1HENST00000711451.1 linkn.2175T>C non_coding_transcript_exon_variant Exon 10 of 36 ENSP00000518763.1
CACNA1HENST00000711452.1 linkn.2175T>C non_coding_transcript_exon_variant Exon 10 of 36 ENSP00000518764.1
CACNA1HENST00000711453.1 linkn.2175T>C non_coding_transcript_exon_variant Exon 10 of 36 ENSP00000518765.1
CACNA1HENST00000711484.1 linkn.2175T>C non_coding_transcript_exon_variant Exon 10 of 35 ENSP00000518773.1
CACNA1HENST00000711486.1 linkn.2175T>C non_coding_transcript_exon_variant Exon 10 of 37 ENSP00000518775.1
CACNA1HENST00000711487.1 linkn.2175T>C non_coding_transcript_exon_variant Exon 10 of 36 ENSP00000518776.1
CACNA1HENST00000711488.1 linkn.2175T>C non_coding_transcript_exon_variant Exon 10 of 35 ENSP00000518777.1
CACNA1HENST00000640028.1 linkn.*88T>C 3_prime_UTR_variant Exon 10 of 35 5 ENSP00000491488.1
CACNA1HENST00000711442.1 linkn.*1622T>C 3_prime_UTR_variant Exon 9 of 34 ENSP00000518758.1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459992
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726276
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33472
American (AMR)
AF:
0.00
AC:
0
AN:
44682
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26114
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39686
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86220
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52056
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
9.00e-7
AC:
1
AN:
1111680
Other (OTH)
AF:
0.00
AC:
0
AN:
60316
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
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.094
DANN
Benign
0.40
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: rs1427937474; hg19: chr16-1254182; API