22-39671635-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021096.4(CACNA1I):​c.4540-564G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,958 control chromosomes in the GnomAD database, including 21,782 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 0.52 ( 21782 hom., cov: 32)

Consequence

CACNA1I
NM_021096.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0810

Publications

7 publications found
Variant links:
Genes affected
CACNA1I (HGNC:1396): (calcium voltage-gated channel subunit alpha1 I) This gene encodes the pore-forming alpha subunit of a voltage gated calcium channel. The encoded protein is a member of a subfamily of calcium channels referred to as is a low voltage-activated, T-type, calcium channel. The channel encoded by this protein is characterized by a slower activation and inactivation compared to other T-type calcium channels. This protein may be involved in calcium signaling in neurons. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]
CACNA1I Gene-Disease associations (from GenCC):
  • neurodevelopmental disorder with speech impairment and with or without seizures
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: MODERATE Submitted by: Illumina

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1INM_021096.4 linkc.4540-564G>A intron_variant Intron 26 of 36 ENST00000402142.4 NP_066919.2 Q9P0X4-1
CACNA1INM_001003406.2 linkc.4435-564G>A intron_variant Intron 25 of 35 NP_001003406.1 Q9P0X4-4
CACNA1IXM_017029035.3 linkc.2686-564G>A intron_variant Intron 16 of 26 XP_016884524.1
CACNA1IXM_017029036.2 linkc.2686-564G>A intron_variant Intron 16 of 26 XP_016884525.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA1IENST00000402142.4 linkc.4540-564G>A intron_variant Intron 26 of 36 1 NM_021096.4 ENSP00000385019.3 Q9P0X4-1
CACNA1IENST00000404898.5 linkc.4435-564G>A intron_variant Intron 25 of 35 1 ENSP00000384093.1 Q9P0X4-4
CACNA1IENST00000401624.5 linkc.4540-564G>A intron_variant Intron 26 of 35 1 ENSP00000383887.1 Q9P0X4-2
CACNA1IENST00000407673.5 linkc.4435-564G>A intron_variant Intron 25 of 34 1 ENSP00000385680.1 Q9P0X4-3

Frequencies

GnomAD3 genomes
AF:
0.524
AC:
79628
AN:
151838
Hom.:
21751
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.576
Gnomad AMI
AF:
0.636
Gnomad AMR
AF:
0.555
Gnomad ASJ
AF:
0.433
Gnomad EAS
AF:
0.958
Gnomad SAS
AF:
0.555
Gnomad FIN
AF:
0.517
Gnomad MID
AF:
0.418
Gnomad NFE
AF:
0.457
Gnomad OTH
AF:
0.487
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.525
AC:
79709
AN:
151958
Hom.:
21782
Cov.:
32
AF XY:
0.532
AC XY:
39512
AN XY:
74272
show subpopulations
African (AFR)
AF:
0.576
AC:
23850
AN:
41406
American (AMR)
AF:
0.556
AC:
8486
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.433
AC:
1502
AN:
3468
East Asian (EAS)
AF:
0.958
AC:
4965
AN:
5182
South Asian (SAS)
AF:
0.554
AC:
2661
AN:
4804
European-Finnish (FIN)
AF:
0.517
AC:
5456
AN:
10544
Middle Eastern (MID)
AF:
0.429
AC:
126
AN:
294
European-Non Finnish (NFE)
AF:
0.457
AC:
31055
AN:
67958
Other (OTH)
AF:
0.486
AC:
1028
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1890
3780
5671
7561
9451
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
690
1380
2070
2760
3450
<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:
0.480
Hom.:
61385
Bravo
AF:
0.530
Asia WGS
AF:
0.713
AC:
2481
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
6.8
DANN
Benign
0.81
PhyloP100
0.081
Mutation Taster
=100/0
polymorphism (auto)

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: rs5750870; hg19: chr22-40067640; API