Variant 2-181482345-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000885.6(ITGA4):c.841-15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,586,036 control chromosomes in the GnomAD database, including 28,374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2145 hom., cov: 32)

Exomes 𝑓: 0.19 ( 26229 hom. )

Consequence

ITGA4
NM_000885.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.504

Variant links:

Genes affected

ITGA4 (HGNC:6140): (integrin subunit alpha 4) The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 4 subunit. This subunit associates with a beta 1 or beta 7 subunit to form an integrin that may play a role in cell motility and migration. This integrin is a therapeutic target for the treatment of multiple sclerosis, Crohn's disease and inflammatory bowel disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ITGA4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 2-181482345-T-C is Benign according to our data. Variant chr2-181482345-T-C is described in ClinVar as [Benign]. Clinvar id is 1270155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA4	NM_000885.6 link	c.841-15T>C		intron_variant		ENST00000397033.7	NP_000876.3	P13612-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ITGA4	ENST00000397033.7 link	c.841-15T>C	intron_variant	1	NM_000885.6	ENSP00000380227.2	P13612-1
ITGA4	ENST00000233573.6 link	c.841-15T>C	intron_variant	1		ENSP00000233573.6	E7EP60
ITGA4	ENST00000465522.5 link	n.1092-15T>C	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24351

AN:

152052

Hom.:

2143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0889

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.232

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.172

GnomAD3 exomes

AF:

0.172

AC:

38862

AN:

226520

Hom.:

3488

AF XY:

0.175

AC XY:

21546

AN XY:

122802

show subpopulations

Gnomad AFR exome

AF:

0.0895

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.250

Gnomad EAS exome

AF:

0.131

Gnomad SAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.145

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.188

AC:

270003

AN:

1433866

Hom.:

26229

Cov.:

AF XY:

0.189

AC XY:

134399

AN XY:

712340

show subpopulations

Gnomad4 AFR exome

AF:

0.0867

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.247

Gnomad4 EAS exome

AF:

0.126

Gnomad4 SAS exome

AF:

0.165

Gnomad4 FIN exome

AF:

0.147

Gnomad4 NFE exome

AF:

0.197

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.160

AC:

24372

AN:

152170

Hom.:

2145

Cov.:

AF XY:

0.158

AC XY:

11753

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0889

Gnomad4 AMR

AF:

0.150

Gnomad4 ASJ

AF:

0.248

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.155

Gnomad4 NFE

AF:

0.201

Gnomad4 OTH

AF:

0.177

Alfa

AF:

0.147

Hom.:

480

Bravo

AF:

0.158

Asia WGS

AF:

0.172

AC:

598

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 02, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.1

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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