Variant chr3-37494493-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_002207.3(ITGA9):c.545-8C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,596,584 control chromosomes in the GnomAD database, including 265,531 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 (★★).

Frequency

Genomes: 𝑓 0.53 ( 22124 hom., cov: 32)

Exomes 𝑓: 0.57 ( 243407 hom. )

Consequence

ITGA9
NM_002207.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.002356

Clinical Significance

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

Conservation

PhyloP100: 0.286

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 3-37494493-C-G is Benign according to our data. Variant chr3-37494493-C-G is described in ClinVar as [Benign]. Clinvar id is 402987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-37494493-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.775 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.545-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000264741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA9	ENST00000264741.10 linkuse as main transcript	c.545-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002207.3	P1
ITGA9	ENST00000422441.5 linkuse as main transcript	c.545-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.529

AC:

80392

AN:

151992

Hom.:

22116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.408

Gnomad AMI

AF:

0.611

Gnomad AMR

AF:

0.632

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.796

Gnomad SAS

AF:

0.405

Gnomad FIN

AF:

0.501

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.576

Gnomad OTH

AF:

0.531

GnomAD3 exomes

AF:

0.569

AC:

141317

AN:

248342

Hom.:

42225

AF XY:

0.558

AC XY:

74845

AN XY:

134200

show subpopulations

Gnomad AFR exome

AF:

0.406

Gnomad AMR exome

AF:

0.741

Gnomad ASJ exome

AF:

0.444

Gnomad EAS exome

AF:

0.799

Gnomad SAS exome

AF:

0.399

Gnomad FIN exome

AF:

0.502

Gnomad NFE exome

AF:

0.573

Gnomad OTH exome

AF:

0.554

GnomAD4 exome

AF:

0.574

AC:

829399

AN:

1444474

Hom.:

243407

Cov.:

AF XY:

0.567

AC XY:

408074

AN XY:

719362

show subpopulations

Gnomad4 AFR exome

AF:

0.399

Gnomad4 AMR exome

AF:

0.725

Gnomad4 ASJ exome

AF:

0.445

Gnomad4 EAS exome

AF:

0.777

Gnomad4 SAS exome

AF:

0.404

Gnomad4 FIN exome

AF:

0.504

Gnomad4 NFE exome

AF:

0.587

Gnomad4 OTH exome

AF:

0.557

GnomAD4 genome

AF:

0.529

AC:

80429

AN:

152110

Hom.:

22124

Cov.:

AF XY:

0.523

AC XY:

38917

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.408

Gnomad4 AMR

AF:

0.632

Gnomad4 ASJ

AF:

0.444

Gnomad4 EAS

AF:

0.795

Gnomad4 SAS

AF:

0.405

Gnomad4 FIN

AF:

0.501

Gnomad4 NFE

AF:

0.576

Gnomad4 OTH

AF:

0.531

Alfa

AF:

0.546

Hom.:

7507

Bravo

AF:

0.543

Asia WGS

AF:

0.566

AC:

1969

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 -

ITGA9-related disorder

Benign:1

Benign, criteria provided, single submitter

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

BayesDel_noAF

Benign

-0.43

CADD

Benign

8.9

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0024

dbscSNV1_RF

Benign

0.048

SpliceAI score (max)

0.030

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