GeneBe

16-1220205-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000711482.1(CACNA1H):​c.6166C>G​(p.Arg2056Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,404,604 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2056Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 35)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CACNA1H
ENST00000711482.1 missense

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.99

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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1HNM_021098.3 linkc.6273C>G p.Ala2091Ala synonymous_variant Exon 35 of 35 ENST00000348261.11 NP_066921.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA1HENST00000711482.1 linkc.6166C>G p.Arg2056Gly missense_variant Exon 36 of 36 ENSP00000518771.1
CACNA1HENST00000711485.1 linkc.6115C>G p.Arg2039Gly missense_variant Exon 35 of 35 ENSP00000518774.1
CACNA1HENST00000711455.1 linkc.6088C>G p.Arg2030Gly missense_variant Exon 36 of 36 ENSP00000518768.1
CACNA1HENST00000348261.11 linkc.6273C>G p.Ala2091Ala synonymous_variant Exon 35 of 35 1 NM_021098.3 ENSP00000334198.7
CACNA1HENST00000569107.6 linkc.6288C>G p.Ala2096Ala synonymous_variant Exon 34 of 34 1 ENSP00000454990.2
CACNA1HENST00000711493.1 linkc.6258C>G p.Ala2086Ala synonymous_variant Exon 34 of 34 ENSP00000518778.1
CACNA1HENST00000565831.7 linkc.6255C>G p.Ala2085Ala synonymous_variant Exon 34 of 34 1 ENSP00000455840.1
CACNA1HENST00000711450.1 linkc.6255C>G p.Ala2085Ala synonymous_variant Exon 35 of 35 ENSP00000518762.1
CACNA1HENST00000564231.6 linkc.6240C>G p.Ala2080Ala synonymous_variant Exon 35 of 35 1 ENSP00000457555.2
CACNA1HENST00000638323.1 linkc.6234C>G p.Ala2078Ala synonymous_variant Exon 35 of 35 5 ENSP00000492267.1
CACNA1HENST00000562079.6 linkc.6222C>G p.Ala2074Ala synonymous_variant Exon 34 of 34 1 ENSP00000454581.2
CACNA1HENST00000711438.1 linkc.6216C>G p.Ala2072Ala synonymous_variant Exon 34 of 34 ENSP00000518754.1
CACNA1HENST00000637236.3 linkn.*2192C>G non_coding_transcript_exon_variant Exon 34 of 34 5 ENSP00000492650.2
CACNA1HENST00000639478.1 linkn.*1321C>G non_coding_transcript_exon_variant Exon 35 of 35 5 ENSP00000491945.1
CACNA1HENST00000640028.1 linkn.*4091C>G non_coding_transcript_exon_variant Exon 35 of 35 5 ENSP00000491488.1
CACNA1HENST00000711442.1 linkn.*5717C>G non_coding_transcript_exon_variant Exon 33 of 34 ENSP00000518758.1
CACNA1HENST00000711448.1 linkn.*1214C>G non_coding_transcript_exon_variant Exon 36 of 36 ENSP00000518760.1
CACNA1HENST00000711449.1 linkn.*1132C>G non_coding_transcript_exon_variant Exon 35 of 35 ENSP00000518761.1
CACNA1HENST00000711451.1 linkn.*1852C>G non_coding_transcript_exon_variant Exon 36 of 36 ENSP00000518763.1
CACNA1HENST00000711452.1 linkn.*940C>G non_coding_transcript_exon_variant Exon 36 of 36 ENSP00000518764.1
CACNA1HENST00000711453.1 linkn.*907C>G non_coding_transcript_exon_variant Exon 36 of 36 ENSP00000518765.1
CACNA1HENST00000711484.1 linkn.*187C>G non_coding_transcript_exon_variant Exon 34 of 35 ENSP00000518773.1
CACNA1HENST00000711486.1 linkn.6273C>G non_coding_transcript_exon_variant Exon 35 of 37 ENSP00000518775.1
CACNA1HENST00000711487.1 linkn.6240C>G non_coding_transcript_exon_variant Exon 35 of 36 ENSP00000518776.1
CACNA1HENST00000711488.1 linkn.*1389C>G non_coding_transcript_exon_variant Exon 35 of 35 ENSP00000518777.1
CACNA1HENST00000711483.1 linkc.*187C>G 3_prime_UTR_variant Exon 35 of 35 ENSP00000518772.1
CACNA1HENST00000711456.1 linkc.*187C>G 3_prime_UTR_variant Exon 34 of 34 ENSP00000518769.1
CACNA1HENST00000637236.3 linkn.*2192C>G 3_prime_UTR_variant Exon 34 of 34 5 ENSP00000492650.2
CACNA1HENST00000639478.1 linkn.*1321C>G 3_prime_UTR_variant Exon 35 of 35 5 ENSP00000491945.1
CACNA1HENST00000640028.1 linkn.*4091C>G 3_prime_UTR_variant Exon 35 of 35 5 ENSP00000491488.1
CACNA1HENST00000711442.1 linkn.*5717C>G 3_prime_UTR_variant Exon 33 of 34 ENSP00000518758.1
CACNA1HENST00000711448.1 linkn.*1214C>G 3_prime_UTR_variant Exon 36 of 36 ENSP00000518760.1
CACNA1HENST00000711449.1 linkn.*1132C>G 3_prime_UTR_variant Exon 35 of 35 ENSP00000518761.1
CACNA1HENST00000711451.1 linkn.*1852C>G 3_prime_UTR_variant Exon 36 of 36 ENSP00000518763.1
CACNA1HENST00000711452.1 linkn.*940C>G 3_prime_UTR_variant Exon 36 of 36 ENSP00000518764.1
CACNA1HENST00000711453.1 linkn.*907C>G 3_prime_UTR_variant Exon 36 of 36 ENSP00000518765.1
CACNA1HENST00000711484.1 linkn.*187C>G 3_prime_UTR_variant Exon 34 of 35 ENSP00000518773.1
CACNA1HENST00000711488.1 linkn.*1389C>G 3_prime_UTR_variant Exon 35 of 35 ENSP00000518777.1
CACNA1HENST00000621827.2 linkn.6121+152C>G intron_variant Intron 35 of 36 6 ENSP00000518766.1

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD4 exome
AF:
7.12e-7
AC:
1
AN:
1404604
Hom.:
0
Cov.:
73
AF XY:
0.00
AC XY:
0
AN XY:
695958
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
29630
American (AMR)
AF:
0.00
AC:
0
AN:
37424
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23484
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36802
South Asian (SAS)
AF:
0.00
AC:
0
AN:
78862
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
45888
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5580
European-Non Finnish (NFE)
AF:
9.18e-7
AC:
1
AN:
1088908
Other (OTH)
AF:
0.00
AC:
0
AN:
58026
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.012
DANN
Benign
0.43
PhyloP100
-5.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs59297244; hg19: chr16-1270205; API