Genetic Variant ITGA9:p.Val788Met (chr3-37743963-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

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

The NM_002207.3(ITGA9):c.2362G>A(p.Val788Met) variant causes a missense change. The variant allele was found at a frequency of 0.00358 in 1,613,984 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0027 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0037 ( 18 hom. )

Consequence

ITGA9
NM_002207.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.11

Variant links:

Genes affected

ITGA9 (HGNC:6145): (integrin subunit alpha 9) This gene encodes an alpha integrin. Integrins are heterodimeric integral membrane glycoproteins composed of an alpha chain and a beta chain that mediate cell-cell and cell-matrix adhesion. The protein encoded by this gene, when bound to the beta 1 chain, forms an integrin that is a receptor for VCAM1, cytotactin and osteopontin. Expression of this gene has been found to be upregulated in small cell lung cancers. [provided by RefSeq, Jul 2008]

ITGA9 links:

ITGA9-AS1 (HGNC:49668): (ITGA9 antisense RNA 1)

ITGA9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009117633).

BP6

Variant 3-37743963-G-A is Benign according to our data. Variant chr3-37743963-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3037361.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-37743963-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA9	NM_002207.3 link	c.2362G>A	p.Val788Met	missense_variant	Exon 22 of 28	ENST00000264741.10	NP_002198.2	Q13797Q8N6H6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA9	ENST00000264741.10 link	c.2362G>A	p.Val788Met	missense_variant	Exon 22 of 28	1	NM_002207.3	ENSP00000264741.5		Q13797

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

418

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00445

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00300

AC:

753

AN:

251358

Hom.:

AF XY:

0.00309

AC XY:

420

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00448

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00419

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00367

AC:

5363

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

2643

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00440

Gnomad4 ASJ exome

AF:

0.00145

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00223

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00420

Gnomad4 OTH exome

AF:

0.00305

GnomAD4 genome

AF:

0.00274

AC:

418

AN:

152310

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

181

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00445

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00395

Hom.:

Bravo

AF:

0.00275

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00581

AC:

ExAC

AF:

0.00265

AC:

322

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00420

EpiControl

AF:

0.00581

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ITGA9-related disorder

Benign:1

May 21, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Benign

0.070

Eigen_PC

Benign

0.038

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.81

M_CAP

Benign

0.031

MetaRNN

Benign

0.0091

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.91

REVEL

Benign

0.12

Sift

Benign

0.097

Sift4G

Benign

0.094

Polyphen

0.95

Vest4

0.33

MVP

0.44

MPC

0.33

ClinPred

0.016

GERP RS

2.8

Varity_R

0.045

gMVP

0.48

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