Variant 2-181534370-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The ENST00000397033.7(ITGA4):c.2883T>C(p.His961His) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 1,522,244 control chromosomes in the GnomAD database, including 268,253 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 27810 hom., cov: 31)

Exomes 𝑓: 0.59 ( 240443 hom. )

Consequence

ITGA4
ENST00000397033.7 splice_region, synonymous

Scores

Splicing: ADA: 0.0007010

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.518

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP7

Synonymous conserved (PhyloP=-0.518 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA4	NM_000885.6 linkuse as main transcript	c.2883T>C	p.His961His	splice_region_variant, synonymous_variant	26/28	ENST00000397033.7	NP_000876.3	P13612-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA4	ENST00000397033.7 linkuse as main transcript	c.2883T>C	p.His961His	splice_region_variant, synonymous_variant	26/28	1	NM_000885.6	ENSP00000380227.2		P13612-1

Frequencies

GnomAD3 genomes

AF:

0.602

AC:

91404

AN:

151852

Hom.:

27797

Cov.:

show subpopulations

Gnomad AFR

AF:

0.635

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.616

Gnomad ASJ

AF:

0.609

Gnomad EAS

AF:

0.632

Gnomad SAS

AF:

0.831

Gnomad FIN

AF:

0.507

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.576

Gnomad OTH

AF:

0.624

GnomAD3 exomes

AF:

0.614

AC:

151532

AN:

246678

Hom.:

47667

AF XY:

0.625

AC XY:

83721

AN XY:

133858

show subpopulations

Gnomad AFR exome

AF:

0.630

Gnomad AMR exome

AF:

0.604

Gnomad ASJ exome

AF:

0.603

Gnomad EAS exome

AF:

0.636

Gnomad SAS exome

AF:

0.835

Gnomad FIN exome

AF:

0.486

Gnomad NFE exome

AF:

0.578

Gnomad OTH exome

AF:

0.610

GnomAD4 exome

AF:

0.587

AC:

804468

AN:

1370274

Hom.:

240443

Cov.:

AF XY:

0.597

AC XY:

410117

AN XY:

687016

show subpopulations

Gnomad4 AFR exome

AF:

0.635

Gnomad4 AMR exome

AF:

0.606

Gnomad4 ASJ exome

AF:

0.610

Gnomad4 EAS exome

AF:

0.618

Gnomad4 SAS exome

AF:

0.837

Gnomad4 FIN exome

AF:

0.490

Gnomad4 NFE exome

AF:

0.566

Gnomad4 OTH exome

AF:

0.596

GnomAD4 genome

AF:

0.602

AC:

91470

AN:

151970

Hom.:

27810

Cov.:

AF XY:

0.604

AC XY:

44855

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.635

Gnomad4 AMR

AF:

0.617

Gnomad4 ASJ

AF:

0.609

Gnomad4 EAS

AF:

0.633

Gnomad4 SAS

AF:

0.831

Gnomad4 FIN

AF:

0.507

Gnomad4 NFE

AF:

0.576

Gnomad4 OTH

AF:

0.620

Alfa

AF:

0.586

Hom.:

52682

Bravo

AF:

0.606

Asia WGS

AF:

0.680

AC:

2363

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.42

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00070

dbscSNV1_RF

Benign

0.058

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