Variant 22-39600512-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000402142.4(CACNA1I):c.349-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000515 in 1,610,294 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 1 hom. )

Consequence

CACNA1I
ENST00000402142.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003778

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.193

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 22-39600512-C-T is Benign according to our data. Variant chr22-39600512-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3040784.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1I	NM_021096.4 linkuse as main transcript	c.349-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000402142.4	NP_066919.2
CACNA1I	NM_001003406.2 linkuse as main transcript	c.349-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001003406.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
CACNA1I	ENST00000402142.4 linkuse as main transcript	c.349-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_021096.4	ENSP00000385019	A2	Q9P0X4-1
CACNA1I	ENST00000401624.5 linkuse as main transcript	c.349-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000383887	P4	Q9P0X4-2
CACNA1I	ENST00000404898.5 linkuse as main transcript	c.349-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000384093	A2	Q9P0X4-4
CACNA1I	ENST00000407673.5 linkuse as main transcript	c.349-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000385680	A2	Q9P0X4-3

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000490

AC:

AN:

245134

Hom.:

AF XY:

0.0000376

AC XY:

AN XY:

133120

show subpopulations

Gnomad AFR exome

AF:

0.000456

Gnomad AMR exome

AF:

0.0000899

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000459

AC:

AN:

1458170

Hom.:

Cov.:

AF XY:

0.0000400

AC XY:

AN XY:

725268

show subpopulations

Gnomad4 AFR exome

AF:

0.000960

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000468

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000105

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.0000982

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CACNA1I-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as likely 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

-0.78

CADD

Benign

4.6

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000038

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.030

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