rs2507940

Variant names:

• chr3-37494493-C-G
• rs2507940
• NM_002207.3:c.545-8C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-37494493-C-G
• chr3-37494493-C-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_002207.3(ITGA9):​c.545-8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 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, intron
• Scores: Splicing: ADA: 0.002356
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.286
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 402987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
ITGA9	NM_002207.3	c.545-8C>G		splice_region_variant, intron_variant	Intron 4 of 27	ENST00000264741.10	NP_002198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA9	ENST00000264741.10	c.545-8C>G		splice_region_variant, intron_variant	Intron 4 of 27	1	NM_002207.3	ENSP00000264741.5
ITGA9	ENST00000422441.5	c.545-8C>G		splice_region_variant, intron_variant	Intron 4 of 15	1		ENSP00000397258.1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80392 AN: 151992 Hom.: 22116 Cov.: 32

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

GnomAD2 exomes AF: 0.569 AC: 141317 AN: 248342 AF XY: 0.558

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 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.: 30 AF XY: 0.567 AC XY: 408074 AN XY: 719362

African (AFR) AF: 0.399 AC: 13249 AN: 33184

American (AMR) AF: 0.725 AC: 32300 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 11561 AN: 26008

East Asian (EAS) AF: 0.777 AC: 30776 AN: 39596

South Asian (SAS) AF: 0.404 AC: 34682 AN: 85766

European-Finnish (FIN) AF: 0.504 AC: 26850 AN: 53270

Middle Eastern (MID) AF: 0.431 AC: 2474 AN: 5736

European-Non Finnish (NFE) AF: 0.587 AC: 644218 AN: 1096550

Other (OTH) AF: 0.557 AC: 33289 AN: 59812

GnomAD4 genome AF: 0.529 AC: 80429 AN: 152110 Hom.: 22124 Cov.: 32 AF XY: 0.523 AC XY: 38917 AN XY: 74346

African (AFR) AF: 0.408 AC: 16925 AN: 41502

American (AMR) AF: 0.632 AC: 9669 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1539 AN: 3468

East Asian (EAS) AF: 0.795 AC: 4103 AN: 5158

South Asian (SAS) AF: 0.405 AC: 1949 AN: 4812

European-Finnish (FIN) AF: 0.501 AC: 5298 AN: 10574

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39166 AN: 67990

Other (OTH) AF: 0.531 AC: 1121 AN: 2110

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

ITGA9-related disorder Benign:1

Aug 02, 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	-0.43
CADD	Benign	8.9
DANN	Benign	0.87
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2507940; hg19: chr3-37535984;