Variant 3-37471115-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002207.3(ITGA9):c.294C>A(p.Thr98=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00522 in 1,613,906 control chromosomes in the GnomAD database, including 274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 146 hom., cov: 31)

Exomes 𝑓: 0.0032 ( 128 hom. )

Consequence

ITGA9
NM_002207.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.50

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 3-37471115-C-A is Benign according to our data. Variant chr3-37471115-C-A is described in ClinVar as [Benign]. Clinvar id is 702082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-37471115-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.5 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA9	NM_002207.3 linkuse as main transcript	c.294C>A	p.Thr98=	synonymous_variant	2/28	ENST00000264741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA9	ENST00000264741.10 linkuse as main transcript	c.294C>A	p.Thr98=	synonymous_variant	2/28	1	NM_002207.3	P1
ITGA9	ENST00000422441.5 linkuse as main transcript	c.294C>A	p.Thr98=	synonymous_variant	2/16	1

Frequencies

GnomAD3 genomes

AF:

0.0248

AC:

3771

AN:

151996

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.00736

AC:

1852

AN:

251470

Hom.:

AF XY:

0.00578

AC XY:

785

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0813

Gnomad AMR exome

AF:

0.00642

Gnomad ASJ exome

AF:

0.0169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000826

Gnomad OTH exome

AF:

0.00701

GnomAD4 exome

AF:

0.00318

AC:

4653

AN:

1461792

Hom.:

128

Cov.:

AF XY:

0.00286

AC XY:

2082

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.0839

Gnomad4 AMR exome

AF:

0.00707

Gnomad4 ASJ exome

AF:

0.0174

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000476

Gnomad4 OTH exome

AF:

0.00793

GnomAD4 genome

AF:

0.0248

AC:

3769

AN:

152114

Hom.:

146

Cov.:

AF XY:

0.0236

AC XY:

1757

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0818

Gnomad4 AMR

AF:

0.0139

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000625

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.00942

Hom.:

Bravo

AF:

0.0292

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

ITGA9-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 18, 2020

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

BayesDel_noAF

Benign

-0.30

CADD

Benign

2.8

DANN

Benign

0.69

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