NM_021098.3:c.1120-3delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_021098.3(CACNA1H):​c.1120-3delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,565,108 control chromosomes in the GnomAD database, including 6 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 4 hom. )

Consequence

CACNA1H
NM_021098.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.255

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: Benign. The variant received -10 ACMG points.

BP6
Variant 16-1200706-GC-G is Benign according to our data. Variant chr16-1200706-GC-G is described in ClinVar as [Benign]. Clinvar id is 529657.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00112 (171/152268) while in subpopulation AMR AF = 0.0109 (167/15298). AF 95% confidence interval is 0.00956. There are 2 homozygotes in GnomAd4. There are 106 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High AC in GnomAd4 at 171 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1HNM_021098.3 linkc.1120-3delC splice_region_variant, intron_variant Intron 7 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.1120-9delC intron_variant Intron 7 of 34 1 NM_021098.3 ENSP00000334198.7 O95180-1
CACNA1HENST00000569107.6 linkc.1120-9delC intron_variant Intron 7 of 33 1 ENSP00000454990.2 H3BNT0
CACNA1HENST00000711493.1 linkc.1120-9delC intron_variant Intron 7 of 33 ENSP00000518778.1
CACNA1HENST00000565831.7 linkc.1120-9delC intron_variant Intron 7 of 33 1 ENSP00000455840.1 O95180-2
CACNA1HENST00000711450.1 linkc.1120-9delC intron_variant Intron 7 of 34 ENSP00000518762.1
CACNA1HENST00000564231.6 linkc.1120-9delC intron_variant Intron 7 of 34 1 ENSP00000457555.2 H3BUA8
CACNA1HENST00000638323.1 linkc.1081-9delC intron_variant Intron 7 of 34 5 ENSP00000492267.1 A0A1W2PR14
CACNA1HENST00000562079.6 linkc.1120-9delC intron_variant Intron 7 of 33 1 ENSP00000454581.2 H3BMW6
CACNA1HENST00000711438.1 linkc.1081-9delC intron_variant Intron 7 of 33 ENSP00000518754.1
CACNA1HENST00000711482.1 linkc.1120-9delC intron_variant Intron 7 of 35 ENSP00000518771.1
CACNA1HENST00000711485.1 linkc.1120-9delC intron_variant Intron 7 of 34 ENSP00000518774.1
CACNA1HENST00000711455.1 linkc.1120-9delC intron_variant Intron 7 of 35 ENSP00000518768.1
CACNA1HENST00000711483.1 linkc.1120-9delC intron_variant Intron 7 of 34 ENSP00000518772.1
CACNA1HENST00000711456.1 linkc.1120-9delC intron_variant Intron 7 of 33 ENSP00000518769.1
CACNA1HENST00000621827.2 linkn.1120-9delC intron_variant Intron 7 of 36 6 ENSP00000518766.1
CACNA1HENST00000637236.3 linkn.1120-9delC intron_variant Intron 7 of 33 5 ENSP00000492650.2 A0A1W2PS38
CACNA1HENST00000639478.1 linkn.1120-9delC intron_variant Intron 7 of 34 5 ENSP00000491945.1 A0A1W2PQW2
CACNA1HENST00000640028.1 linkn.1120-9delC intron_variant Intron 7 of 34 5 ENSP00000491488.1 A0A1W2PQ19
CACNA1HENST00000711442.1 linkn.*567-9delC intron_variant Intron 6 of 33 ENSP00000518758.1
CACNA1HENST00000711448.1 linkn.1120-9delC intron_variant Intron 7 of 35 ENSP00000518760.1
CACNA1HENST00000711449.1 linkn.1120-9delC intron_variant Intron 7 of 34 ENSP00000518761.1
CACNA1HENST00000711451.1 linkn.1120-9delC intron_variant Intron 7 of 35 ENSP00000518763.1
CACNA1HENST00000711452.1 linkn.1120-9delC intron_variant Intron 7 of 35 ENSP00000518764.1
CACNA1HENST00000711453.1 linkn.1120-9delC intron_variant Intron 7 of 35 ENSP00000518765.1
CACNA1HENST00000711484.1 linkn.1120-9delC intron_variant Intron 7 of 34 ENSP00000518773.1
CACNA1HENST00000711486.1 linkn.1120-9delC intron_variant Intron 7 of 36 ENSP00000518775.1
CACNA1HENST00000711487.1 linkn.1120-9delC intron_variant Intron 7 of 35 ENSP00000518776.1
CACNA1HENST00000711488.1 linkn.1120-9delC intron_variant Intron 7 of 34 ENSP00000518777.1

Frequencies

GnomAD3 genomes
AF:
0.00112
AC:
171
AN:
152150
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0109
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:
0.00
Gnomad OTH
AF:
0.000957
GnomAD2 exomes
AF:
0.000628
AC:
109
AN:
173676
AF XY:
0.000664
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00398
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000823
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000210
GnomAD4 exome
AF:
0.000113
AC:
160
AN:
1412840
Hom.:
4
Cov.:
33
AF XY:
0.000130
AC XY:
91
AN XY:
698664
show subpopulations
African (AFR)
AF:
0.0000624
AC:
2
AN:
32052
American (AMR)
AF:
0.00378
AC:
141
AN:
37256
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25334
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36620
South Asian (SAS)
AF:
0.0000984
AC:
8
AN:
81308
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49262
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5508
European-Non Finnish (NFE)
AF:
0.00000276
AC:
3
AN:
1086920
Other (OTH)
AF:
0.000102
AC:
6
AN:
58580
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.512
Heterozygous variant carriers
0
11
22
32
43
54
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:
0.00112
AC:
171
AN:
152268
Hom.:
2
Cov.:
32
AF XY:
0.00142
AC XY:
106
AN XY:
74452
show subpopulations
African (AFR)
AF:
0.0000482
AC:
2
AN:
41536
American (AMR)
AF:
0.0109
AC:
167
AN:
15298
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5174
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68024
Other (OTH)
AF:
0.000947
AC:
2
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.512
Heterozygous variant carriers
0
9
17
26
34
43
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome 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
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00137

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Idiopathic generalized epilepsy;C4310756:Hyperaldosteronism, familial, type IV Benign:1
Feb 02, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.26
Mutation Taster
=100/0
polymorphism

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: rs748730819; hg19: chr16-1250706; COSMIC: COSV100670572; COSMIC: COSV100670572; API