Variant chr2-181530618-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000885.6(ITGA4):c.2633G>A(p.Arg878Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 1,611,264 control chromosomes in the GnomAD database, including 397,059 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.72 ( 39732 hom., cov: 32)

Exomes 𝑓: 0.70 ( 357327 hom. )

Consequence

ITGA4
NM_000885.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.93

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.6516366E-7).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA4	NM_000885.6 linkuse as main transcript	c.2633G>A	p.Arg878Gln	missense_variant	24/28	ENST00000397033.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA4	ENST00000397033.7 linkuse as main transcript	c.2633G>A	p.Arg878Gln	missense_variant	24/28	1	NM_000885.6	P1	P13612-1

Frequencies

GnomAD3 genomes

AF:

0.719

AC:

109299

AN:

151982

Hom.:

39708

Cov.:

show subpopulations

Gnomad AFR

AF:

0.751

Gnomad AMI

AF:

0.428

Gnomad AMR

AF:

0.777

Gnomad ASJ

AF:

0.672

Gnomad EAS

AF:

0.851

Gnomad SAS

AF:

0.888

Gnomad FIN

AF:

0.696

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.675

Gnomad OTH

AF:

0.714

GnomAD3 exomes

AF:

0.738

AC:

183880

AN:

249130

Hom.:

68695

AF XY:

0.741

AC XY:

100122

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.753

Gnomad AMR exome

AF:

0.807

Gnomad ASJ exome

AF:

0.665

Gnomad EAS exome

AF:

0.847

Gnomad SAS exome

AF:

0.884

Gnomad FIN exome

AF:

0.684

Gnomad NFE exome

AF:

0.676

Gnomad OTH exome

AF:

0.727

GnomAD4 exome

AF:

0.697

AC:

1017040

AN:

1459164

Hom.:

357327

Cov.:

AF XY:

0.703

AC XY:

510373

AN XY:

725984

show subpopulations

Gnomad4 AFR exome

AF:

0.753

Gnomad4 AMR exome

AF:

0.803

Gnomad4 ASJ exome

AF:

0.671

Gnomad4 EAS exome

AF:

0.840

Gnomad4 SAS exome

AF:

0.885

Gnomad4 FIN exome

AF:

0.688

Gnomad4 NFE exome

AF:

0.672

Gnomad4 OTH exome

AF:

0.706

GnomAD4 genome

AF:

0.719

AC:

109377

AN:

152100

Hom.:

39732

Cov.:

AF XY:

0.726

AC XY:

53968

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.750

Gnomad4 AMR

AF:

0.777

Gnomad4 ASJ

AF:

0.672

Gnomad4 EAS

AF:

0.851

Gnomad4 SAS

AF:

0.888

Gnomad4 FIN

AF:

0.696

Gnomad4 NFE

AF:

0.675

Gnomad4 OTH

AF:

0.713

Alfa

AF:

0.689

Hom.:

64346

Bravo

AF:

0.721

TwinsUK

AF:

0.660

AC:

2448

ALSPAC

AF:

0.663

AC:

2554

ESP6500AA

AF:

0.752

AC:

2847

ESP6500EA

AF:

0.678

AC:

5596

ExAC

AF:

0.737

AC:

88991

Asia WGS

AF:

0.846

AC:

2941

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.032

DANN

Benign

0.84

DEOGEN2

Benign

0.11

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.13

MetaRNN

Benign

8.7e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.41

MutationTaster

Benign

1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.020

REVEL

Benign

0.023

Sift

Benign

0.38

Sift4G

Benign

0.47

Polyphen

0.063

Vest4

0.020

MPC

0.13

ClinPred

0.024

GERP RS

-11

Varity_R

0.014

gMVP

0.33

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over