GeneBe

rs3751889

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.6123T>A​(p.Gly2041Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G2041G) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.98

Publications

11 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=-0.9).
BP7
Synonymous conserved (PhyloP=-3.98 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1HNM_021098.3 linkc.6123T>A p.Gly2041Gly synonymous_variant Exon 35 of 35 ENST00000348261.11 NP_066921.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA1HENST00000348261.11 linkc.6123T>A p.Gly2041Gly synonymous_variant Exon 35 of 35 1 NM_021098.3 ENSP00000334198.7
CACNA1HENST00000569107.6 linkc.6138T>A p.Gly2046Gly synonymous_variant Exon 34 of 34 1 ENSP00000454990.2
CACNA1HENST00000711493.1 linkc.6108T>A p.Gly2036Gly synonymous_variant Exon 34 of 34 ENSP00000518778.1
CACNA1HENST00000565831.7 linkc.6105T>A p.Gly2035Gly synonymous_variant Exon 34 of 34 1 ENSP00000455840.1
CACNA1HENST00000711450.1 linkc.6105T>A p.Gly2035Gly synonymous_variant Exon 35 of 35 ENSP00000518762.1
CACNA1HENST00000564231.6 linkc.6090T>A p.Gly2030Gly synonymous_variant Exon 35 of 35 1 ENSP00000457555.2
CACNA1HENST00000638323.1 linkc.6084T>A p.Gly2028Gly synonymous_variant Exon 35 of 35 5 ENSP00000492267.1
CACNA1HENST00000562079.6 linkc.6072T>A p.Gly2024Gly synonymous_variant Exon 34 of 34 1 ENSP00000454581.2
CACNA1HENST00000711438.1 linkc.6066T>A p.Gly2022Gly synonymous_variant Exon 34 of 34 ENSP00000518754.1
CACNA1HENST00000637236.3 linkn.*2042T>A non_coding_transcript_exon_variant Exon 34 of 34 5 ENSP00000492650.2
CACNA1HENST00000639478.1 linkn.*1171T>A non_coding_transcript_exon_variant Exon 35 of 35 5 ENSP00000491945.1
CACNA1HENST00000640028.1 linkn.*3941T>A non_coding_transcript_exon_variant Exon 35 of 35 5 ENSP00000491488.1
CACNA1HENST00000711442.1 linkn.*5567T>A non_coding_transcript_exon_variant Exon 33 of 34 ENSP00000518758.1
CACNA1HENST00000711448.1 linkn.*1064T>A non_coding_transcript_exon_variant Exon 36 of 36 ENSP00000518760.1
CACNA1HENST00000711449.1 linkn.*982T>A non_coding_transcript_exon_variant Exon 35 of 35 ENSP00000518761.1
CACNA1HENST00000711451.1 linkn.*1702T>A non_coding_transcript_exon_variant Exon 36 of 36 ENSP00000518763.1
CACNA1HENST00000711452.1 linkn.*790T>A non_coding_transcript_exon_variant Exon 36 of 36 ENSP00000518764.1
CACNA1HENST00000711453.1 linkn.*757T>A non_coding_transcript_exon_variant Exon 36 of 36 ENSP00000518765.1
CACNA1HENST00000711484.1 linkn.*37T>A non_coding_transcript_exon_variant Exon 34 of 35 ENSP00000518773.1
CACNA1HENST00000711486.1 linkn.6123T>A non_coding_transcript_exon_variant Exon 35 of 37 ENSP00000518775.1
CACNA1HENST00000711487.1 linkn.6090T>A non_coding_transcript_exon_variant Exon 35 of 36 ENSP00000518776.1
CACNA1HENST00000711488.1 linkn.*1239T>A non_coding_transcript_exon_variant Exon 35 of 35 ENSP00000518777.1
CACNA1HENST00000711483.1 linkc.*37T>A 3_prime_UTR_variant Exon 35 of 35 ENSP00000518772.1
CACNA1HENST00000711456.1 linkc.*37T>A 3_prime_UTR_variant Exon 34 of 34 ENSP00000518769.1
CACNA1HENST00000637236.3 linkn.*2042T>A 3_prime_UTR_variant Exon 34 of 34 5 ENSP00000492650.2
CACNA1HENST00000639478.1 linkn.*1171T>A 3_prime_UTR_variant Exon 35 of 35 5 ENSP00000491945.1
CACNA1HENST00000640028.1 linkn.*3941T>A 3_prime_UTR_variant Exon 35 of 35 5 ENSP00000491488.1
CACNA1HENST00000711442.1 linkn.*5567T>A 3_prime_UTR_variant Exon 33 of 34 ENSP00000518758.1
CACNA1HENST00000711448.1 linkn.*1064T>A 3_prime_UTR_variant Exon 36 of 36 ENSP00000518760.1
CACNA1HENST00000711449.1 linkn.*982T>A 3_prime_UTR_variant Exon 35 of 35 ENSP00000518761.1
CACNA1HENST00000711451.1 linkn.*1702T>A 3_prime_UTR_variant Exon 36 of 36 ENSP00000518763.1
CACNA1HENST00000711452.1 linkn.*790T>A 3_prime_UTR_variant Exon 36 of 36 ENSP00000518764.1
CACNA1HENST00000711453.1 linkn.*757T>A 3_prime_UTR_variant Exon 36 of 36 ENSP00000518765.1
CACNA1HENST00000711484.1 linkn.*37T>A 3_prime_UTR_variant Exon 34 of 35 ENSP00000518773.1
CACNA1HENST00000711488.1 linkn.*1239T>A 3_prime_UTR_variant Exon 35 of 35 ENSP00000518777.1
CACNA1HENST00000711482.1 linkc.6121+2T>A splice_donor_variant, intron_variant Intron 35 of 35 ENSP00000518771.1
CACNA1HENST00000711485.1 linkc.6070+2T>A splice_donor_variant, intron_variant Intron 34 of 34 ENSP00000518774.1
CACNA1HENST00000711455.1 linkc.6043+2T>A splice_donor_variant, intron_variant Intron 35 of 35 ENSP00000518768.1
CACNA1HENST00000621827.2 linkn.6121+2T>A splice_donor_variant, intron_variant Intron 35 of 36 6 ENSP00000518766.1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1275028
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
618342
African (AFR)
AF:
0.00
AC:
0
AN:
25374
American (AMR)
AF:
0.00
AC:
0
AN:
19692
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
17826
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30946
South Asian (SAS)
AF:
0.00
AC:
0
AN:
54094
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
45862
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5116
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1023594
Other (OTH)
AF:
0.00
AC:
0
AN:
52524
GnomAD4 genome
Cov.:
34
Alfa
AF:
0.00
Hom.:
153
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.027
DANN
Benign
0.51
PhyloP100
-4.0

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: rs3751889; hg19: chr16-1270055; API