Variant rs60192012 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021096.4(CACNA1I):c.20C>A(p.Pro7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,608,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CACNA1I
NM_021096.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0490

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.084708214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1I	NM_021096.4 link	c.20C>A	p.Pro7Gln	missense_variant	Exon 1 of 37	ENST00000402142.4	NP_066919.2	Q9P0X4-1
CACNA1I	NM_001003406.2 link	c.20C>A	p.Pro7Gln	missense_variant	Exon 1 of 36		NP_001003406.1	Q9P0X4-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1I	ENST00000402142.4 link	c.20C>A	p.Pro7Gln	missense_variant	Exon 1 of 37	1	NM_021096.4	ENSP00000385019.3	Q9P0X4-1
CACNA1I	ENST00000404898.5 link	c.20C>A	p.Pro7Gln	missense_variant	Exon 1 of 36	1		ENSP00000384093.1	Q9P0X4-4
CACNA1I	ENST00000401624.5 link	c.20C>A	p.Pro7Gln	missense_variant	Exon 1 of 36	1		ENSP00000383887.1	Q9P0X4-2
CACNA1I	ENST00000407673.5 link	c.20C>A	p.Pro7Gln	missense_variant	Exon 1 of 35	1		ENSP00000385680.1	Q9P0X4-3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455936

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724004

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.017

.;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.45

T;T;T;T

M_CAP

Benign

0.082

MetaRNN

Benign

0.085

T;T;T;T

MetaSVM

Uncertain

-0.10

MutationAssessor

Benign

1.1

L;L;L;L

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.040

D;D;D;D

Sift4G

Benign

0.25

T;T;T;T

Polyphen

0.0010, 0.0

.;.;B;B

Vest4

0.11

MutPred

0.23

Loss of glycosylation at P7 (P = 0.0051);Loss of glycosylation at P7 (P = 0.0051);Loss of glycosylation at P7 (P = 0.0051);Loss of glycosylation at P7 (P = 0.0051);

MVP

0.32

MPC

0.70

ClinPred

0.11

GERP RS

-2.5

Varity_R

0.054

gMVP

0.38

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over