Variant 22-39570772-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_021096.4(CACNA1I):c.20C>T(p.Pro7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00596 in 1,608,158 control chromosomes in the GnomAD database, including 494 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.031 ( 264 hom., cov: 31)

Exomes 𝑓: 0.0033 ( 230 hom. )

Consequence

CACNA1I
NM_021096.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016570389).

BP6

Variant 22-39570772-C-T is Benign according to our data. Variant chr22-39570772-C-T is described in ClinVar as [Benign]. Clinvar id is 3055495.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1I	NM_021096.4 link	c.20C>T	p.Pro7Leu	missense_variant	1/37	ENST00000402142.4	NP_066919.2	Q9P0X4-1
CACNA1I	NM_001003406.2 link	c.20C>T	p.Pro7Leu	missense_variant	1/36		NP_001003406.1	Q9P0X4-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CACNA1I	ENST00000402142.4 link	c.20C>T	p.Pro7Leu	missense_variant	1/37	1	NM_021096.4	ENSP00000385019.3	Q9P0X4-1
CACNA1I	ENST00000404898.5 link	c.20C>T	p.Pro7Leu	missense_variant	1/36	1		ENSP00000384093.1	Q9P0X4-4
CACNA1I	ENST00000401624.5 link	c.20C>T	p.Pro7Leu	missense_variant	1/36	1		ENSP00000383887.1	Q9P0X4-2
CACNA1I	ENST00000407673.5 link	c.20C>T	p.Pro7Leu	missense_variant	1/35	1		ENSP00000385680.1	Q9P0X4-3

Frequencies

GnomAD3 genomes

AF:

0.0309

AC:

4700

AN:

152108

Hom.:

262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.0173

GnomAD3 exomes

AF:

0.00746

AC:

1745

AN:

234048

Hom.:

AF XY:

0.00602

AC XY:

771

AN XY:

128026

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.00387

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000268

Gnomad FIN exome

AF:

0.0000968

Gnomad NFE exome

AF:

0.000425

Gnomad OTH exome

AF:

0.00260

GnomAD4 exome

AF:

0.00334

AC:

4862

AN:

1455932

Hom.:

230

Cov.:

AF XY:

0.00294

AC XY:

2125

AN XY:

724004

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.00459

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000315

Gnomad4 FIN exome

AF:

0.0000575

Gnomad4 NFE exome

AF:

0.000406

Gnomad4 OTH exome

AF:

0.00707

GnomAD4 genome

AF:

0.0310

AC:

4720

AN:

152226

Hom.:

264

Cov.:

AF XY:

0.0295

AC XY:

2199

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.108

Gnomad4 AMR

AF:

0.0102

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.0171

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.0353

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0984

AC:

418

ESP6500EA

AF:

0.000475

AC:

ExAC

AF:

0.00933

AC:

1128

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CACNA1I-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 20, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.025

.;.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.55

T;T;T;T

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.1

L;L;L;L

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.39

T;T;T;T

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.0010

.;.;B;B

Vest4

0.11

MVP

0.30

MPC

0.77

ClinPred

0.0015

GERP RS

-2.5

Varity_R

0.036

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over