Variant chr22-39570851-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The ENST00000402142.4(CACNA1I):c.99C>T(p.Ser33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,613,156 control chromosomes in the GnomAD database, including 83,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.27 ( 6807 hom., cov: 31)

Exomes 𝑓: 0.31 ( 76849 hom. )

Consequence

CACNA1I
ENST00000402142.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.92

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 22-39570851-C-T is Benign according to our data. Variant chr22-39570851-C-T is described in ClinVar as [Benign]. Clinvar id is 3060116.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1I	NM_021096.4 linkuse as main transcript	c.99C>T	p.Ser33=	synonymous_variant	1/37	ENST00000402142.4	NP_066919.2
CACNA1I	NM_001003406.2 linkuse as main transcript	c.99C>T	p.Ser33=	synonymous_variant	1/36		NP_001003406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1I	ENST00000402142.4 linkuse as main transcript	c.99C>T	p.Ser33=	synonymous_variant	1/37	1	NM_021096.4	ENSP00000385019	A2	Q9P0X4-1
CACNA1I	ENST00000404898.5 linkuse as main transcript	c.99C>T	p.Ser33=	synonymous_variant	1/36	1		ENSP00000384093	A2	Q9P0X4-4
CACNA1I	ENST00000401624.5 linkuse as main transcript	c.99C>T	p.Ser33=	synonymous_variant	1/36	1		ENSP00000383887	P4	Q9P0X4-2
CACNA1I	ENST00000407673.5 linkuse as main transcript	c.99C>T	p.Ser33=	synonymous_variant	1/35	1		ENSP00000385680	A2	Q9P0X4-3

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40350

AN:

151876

Hom.:

6799

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0920

Gnomad AMI

AF:

0.283

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.724

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.306

GnomAD3 exomes

AF:

0.324

AC:

80196

AN:

247356

Hom.:

15221

AF XY:

0.323

AC XY:

43421

AN XY:

134526

show subpopulations

Gnomad AFR exome

AF:

0.0849

Gnomad AMR exome

AF:

0.284

Gnomad ASJ exome

AF:

0.302

Gnomad EAS exome

AF:

0.724

Gnomad SAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.388

Gnomad NFE exome

AF:

0.309

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.312

AC:

456224

AN:

1461162

Hom.:

76849

Cov.:

AF XY:

0.311

AC XY:

226156

AN XY:

726892

show subpopulations

Gnomad4 AFR exome

AF:

0.0876

Gnomad4 AMR exome

AF:

0.290

Gnomad4 ASJ exome

AF:

0.307

Gnomad4 EAS exome

AF:

0.744

Gnomad4 SAS exome

AF:

0.266

Gnomad4 FIN exome

AF:

0.387

Gnomad4 NFE exome

AF:

0.304

Gnomad4 OTH exome

AF:

0.321

GnomAD4 genome

AF:

0.266

AC:

40356

AN:

151994

Hom.:

6807

Cov.:

AF XY:

0.272

AC XY:

20219

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.0918

Gnomad4 AMR

AF:

0.292

Gnomad4 ASJ

AF:

0.304

Gnomad4 EAS

AF:

0.725

Gnomad4 SAS

AF:

0.292

Gnomad4 FIN

AF:

0.378

Gnomad4 NFE

AF:

0.308

Gnomad4 OTH

AF:

0.311

Alfa

AF:

0.283

Hom.:

3063

Bravo

AF:

0.257

Asia WGS

AF:

0.436

AC:

1510

AN:

3478

EpiCase

AF:

0.309

EpiControl

AF:

0.301

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

Oct 18, 2019

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

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.84

DANN

Benign

0.55

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