NM_021098.3:c.-18-28G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_021098.3(CACNA1H):​c.-18-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,179,358 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0023 ( 7 hom. )

Consequence

CACNA1H
NM_021098.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0990
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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0019 (286/150356) while in subpopulation NFE AF= 0.00281 (189/67368). AF 95% confidence interval is 0.00248. There are 0 homozygotes in gnomad4. There are 132 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High AC in GnomAd4 at 286 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1HNM_021098.3 linkc.-18-28G>A intron_variant Intron 1 of 34 ENST00000348261.11 NP_066921.2 O95180-1B3KQH9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA1HENST00000348261.11 linkc.-18-28G>A intron_variant Intron 1 of 34 1 NM_021098.3 ENSP00000334198.7 O95180-1
CACNA1HENST00000638323.1 linkc.-18-28G>A intron_variant Intron 1 of 34 5 ENSP00000492267.1 A0A1W2PR14
CACNA1HENST00000639478.1 linkn.-18-28G>A intron_variant Intron 1 of 34 5 ENSP00000491945.1 A0A1W2PQW2
CACNA1HENST00000640028.1 linkn.-18-28G>A intron_variant Intron 1 of 34 5 ENSP00000491488.1 A0A1W2PQ19
CACNA1HENST00000565831.6 linkc.-46G>A upstream_gene_variant 1 ENSP00000455840.1 O95180-2

Frequencies

GnomAD3 genomes
AF:
0.00191
AC:
287
AN:
150258
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.000438
Gnomad AMI
AF:
0.0364
Gnomad AMR
AF:
0.00132
Gnomad ASJ
AF:
0.00406
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00125
Gnomad FIN
AF:
0.000198
Gnomad MID
AF:
0.00658
Gnomad NFE
AF:
0.00281
Gnomad OTH
AF:
0.00145
GnomAD3 exomes
AF:
0.00505
AC:
1
AN:
198
Hom.:
0
AF XY:
0.00893
AC XY:
1
AN XY:
112
show subpopulations
Gnomad NFE exome
AF:
0.00515
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00227
AC:
2333
AN:
1029002
Hom.:
7
Cov.:
28
AF XY:
0.00225
AC XY:
1093
AN XY:
485486
show subpopulations
Gnomad4 AFR exome
AF:
0.000428
Gnomad4 AMR exome
AF:
0.000873
Gnomad4 ASJ exome
AF:
0.00182
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00189
Gnomad4 FIN exome
AF:
0.000101
Gnomad4 NFE exome
AF:
0.00246
Gnomad4 OTH exome
AF:
0.00178
GnomAD4 genome
AF:
0.00190
AC:
286
AN:
150356
Hom.:
0
Cov.:
30
AF XY:
0.00180
AC XY:
132
AN XY:
73426
show subpopulations
Gnomad4 AFR
AF:
0.000437
Gnomad4 AMR
AF:
0.00132
Gnomad4 ASJ
AF:
0.00406
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00125
Gnomad4 FIN
AF:
0.000198
Gnomad4 NFE
AF:
0.00281
Gnomad4 OTH
AF:
0.00144
Alfa
AF:
0.00243
Hom.:
0
Bravo
AF:
0.00193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
16
DANN
Benign
0.78

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs536495319; hg19: chr16-1203692; API