Genetic Variant ITGA9:c.2234+7G>C (chr3-37736990-G-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002207.3(ITGA9):c.2234+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,585,262 control chromosomes in the GnomAD database, including 57,836 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.34 ( 11086 hom., cov: 32)

Exomes 𝑓: 0.25 ( 46750 hom. )

Consequence

ITGA9
NM_002207.3 splice_region, intron

Scores

Splicing: ADA: 0.00002006

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.681

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:

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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=-0.84).

BP6

Variant 3-37736990-G-C is Benign according to our data. Variant chr3-37736990-G-C is described in ClinVar as [Benign]. Clinvar id is 3060254.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-37736990-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA9	NM_002207.3 link	c.2234+7G>C		splice_region_variant, intron_variant	Intron 20 of 27	ENST00000264741.10	NP_002198.2	Q13797Q8N6H6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA9	ENST00000264741.10 link	c.2234+7G>C		splice_region_variant, intron_variant	Intron 20 of 27	1	NM_002207.3	ENSP00000264741.5		Q13797

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52090

AN:

151954

Hom.:

11052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.608

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.250

Gnomad OTH

AF:

0.322

GnomAD3 exomes

AF:

0.252

AC:

63251

AN:

251080

Hom.:

9452

AF XY:

0.249

AC XY:

33836

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.618

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.276

Gnomad EAS exome

AF:

0.180

Gnomad SAS exome

AF:

0.258

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.245

AC:

351549

AN:

1433190

Hom.:

46750

Cov.:

AF XY:

0.246

AC XY:

176030

AN XY:

715002

show subpopulations

Gnomad4 AFR exome

AF:

0.619

Gnomad4 AMR exome

AF:

0.164

Gnomad4 ASJ exome

AF:

0.273

Gnomad4 EAS exome

AF:

0.173

Gnomad4 SAS exome

AF:

0.256

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.239

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.343

AC:

52180

AN:

152072

Hom.:

11086

Cov.:

AF XY:

0.336

AC XY:

25010

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.608

Gnomad4 AMR

AF:

0.241

Gnomad4 ASJ

AF:

0.274

Gnomad4 EAS

AF:

0.181

Gnomad4 SAS

AF:

0.256

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.250

Gnomad4 OTH

AF:

0.322

Alfa

AF:

0.225

Hom.:

1259

Bravo

AF:

0.359

EpiCase

AF:

0.256

EpiControl

AF:

0.254

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ITGA9-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.84

CADD

Benign

1.3

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000020

dbscSNV1_RF

Benign

0.0

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