rs267561

Positions:

Variant summary

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

The NM_002207.3(ITGA9):c.1520G>A(p.Gly507Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,613,482 control chromosomes in the GnomAD database, including 274,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.55 ( 23851 hom., cov: 32)

Exomes 𝑓: 0.58 ( 250743 hom. )

Consequence

ITGA9
NM_002207.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.88

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:

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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 (MetaRNN=1.7952218E-6).

BP6

Variant 3-37533460-G-A is Benign according to our data. Variant chr3-37533460-G-A is described in ClinVar as [Benign]. Clinvar id is 402989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-37533460-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA9	NM_002207.3 linkuse as main transcript	c.1520G>A	p.Gly507Glu	missense_variant	14/28	ENST00000264741.10	NP_002198.2	Q13797Q8N6H6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA9	ENST00000264741.10 linkuse as main transcript	c.1520G>A	p.Gly507Glu	missense_variant	14/28	1	NM_002207.3	ENSP00000264741.5		Q13797
ITGA9	ENST00000422441.5 linkuse as main transcript	c.1520G>A	p.Gly507Glu	missense_variant	14/16	1		ENSP00000397258.1		E9PDS3

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83873

AN:

151892

Hom.:

23825

Cov.:

show subpopulations

Gnomad AFR

AF:

0.463

Gnomad AMI

AF:

0.638

Gnomad AMR

AF:

0.634

Gnomad ASJ

AF:

0.499

Gnomad EAS

AF:

0.812

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.579

Gnomad OTH

AF:

0.539

GnomAD3 exomes

AF:

0.583

AC:

146132

AN:

250708

Hom.:

44450

AF XY:

0.570

AC XY:

77212

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.467

Gnomad AMR exome

AF:

0.740

Gnomad ASJ exome

AF:

0.499

Gnomad EAS exome

AF:

0.813

Gnomad SAS exome

AF:

0.401

Gnomad FIN exome

AF:

0.569

Gnomad NFE exome

AF:

0.575

Gnomad OTH exome

AF:

0.563

GnomAD4 exome

AF:

0.581

AC:

849080

AN:

1461472

Hom.:

250743

Cov.:

AF XY:

0.574

AC XY:

417278

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.460

Gnomad4 AMR exome

AF:

0.724

Gnomad4 ASJ exome

AF:

0.496

Gnomad4 EAS exome

AF:

0.793

Gnomad4 SAS exome

AF:

0.407

Gnomad4 FIN exome

AF:

0.566

Gnomad4 NFE exome

AF:

0.589

Gnomad4 OTH exome

AF:

0.568

GnomAD4 genome

AF:

0.552

AC:

83941

AN:

152010

Hom.:

23851

Cov.:

AF XY:

0.550

AC XY:

40868

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.463

Gnomad4 AMR

AF:

0.635

Gnomad4 ASJ

AF:

0.499

Gnomad4 EAS

AF:

0.812

Gnomad4 SAS

AF:

0.406

Gnomad4 FIN

AF:

0.572

Gnomad4 NFE

AF:

0.579

Gnomad4 OTH

AF:

0.539

Alfa

AF:

0.570

Hom.:

40353

Bravo

AF:

0.562

TwinsUK

AF:

0.595

AC:

2205

ALSPAC

AF:

0.587

AC:

2263

ESP6500AA

AF:

0.471

AC:

2077

ESP6500EA

AF:

0.580

AC:

4991

ExAC

AF:

0.571

AC:

69371

Asia WGS

AF:

0.579

AC:

2016

AN:

3478

EpiCase

AF:

0.562

EpiControl

AF:

0.569

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 57% of total chromosomes in ExAC -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

ITGA9-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 02, 2019

This variant is classified as 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

T;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.0000018

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

.;M

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.27

Sift

Benign

0.031

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

0.53

P;B

Vest4

0.31

MPC

0.40

ClinPred

0.054

GERP RS

5.9

Varity_R

0.53

gMVP

0.73

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