rs2507941

chr3-37494565-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_002207.3(ITGA9):c.609C>T(p.Thr203=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 1,611,664 control chromosomes in the GnomAD database, including 2,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.045 (205 hom., cov: 33)
  • Exomes 𝑓: 0.056 (2527 hom.)
• Consequence: ITGA9 NM_002207.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.91

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 3-37494565-C-T is Benign according to our data. Variant chr3-37494565-C-T is described in ClinVar as [Benign]. Clinvar id is 402988.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-37494565-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA9	NM_002207.3	c.609C>T	p.Thr203=	synonymous_variant	5/28	ENST00000264741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA9	ENST00000264741.10	c.609C>T	p.Thr203=	synonymous_variant	5/28	1	NM_002207.3	P1
ITGA9	ENST00000422441.5	c.609C>T	p.Thr203=	synonymous_variant	5/16	1

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6922 AN: 152172 Hom.: 206 Cov.: 33

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0701

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.0706

Gnomad SAS AF: 0.0466

Gnomad FIN AF: 0.0257

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.0573

GnomAD3 exomes AF: 0.0491 AC: 12312 AN: 250738 Hom.: 328 AF XY: 0.0504 AC XY: 6826 AN XY: 135568

Gnomad AFR exome AF: 0.0147

Gnomad AMR exome AF: 0.0470

Gnomad ASJ exome AF: 0.0369

Gnomad EAS exome AF: 0.0641

Gnomad SAS exome AF: 0.0508

Gnomad FIN exome AF: 0.0259

Gnomad NFE exome AF: 0.0569

Gnomad OTH exome AF: 0.0557

GnomAD4 exome AF: 0.0560 AC: 81797 AN: 1459374 Hom.: 2527 Cov.: 31 AF XY: 0.0557 AC XY: 40454 AN XY: 726126

Gnomad4 AFR exome AF: 0.0135

Gnomad4 AMR exome AF: 0.0490

Gnomad4 ASJ exome AF: 0.0374

Gnomad4 EAS exome AF: 0.0731

Gnomad4 SAS exome AF: 0.0522

Gnomad4 FIN exome AF: 0.0265

Gnomad4 NFE exome AF: 0.0589

Gnomad4 OTH exome AF: 0.0596

GnomAD4 genome AF: 0.0455 AC: 6926 AN: 152290 Hom.: 205 Cov.: 33 AF XY: 0.0454 AC XY: 3382 AN XY: 74456

Gnomad4 AFR AF: 0.0149

Gnomad4 AMR AF: 0.0699

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.0706

Gnomad4 SAS AF: 0.0466

Gnomad4 FIN AF: 0.0257

Gnomad4 NFE AF: 0.0590

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0559 Hom.: 472

Bravo AF: 0.0476

Asia WGS AF: 0.0550 AC: 189 AN: 3478

EpiCase AF: 0.0587

EpiControl AF: 0.0637

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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: 5% of total chromosomes in ExAC -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	5.5
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2507941; hg19: chr3-37536056; COSMIC: COSV53246160;