chr3-37494565-C-T

Variant names:

• chr3-37494565-C-T
• rs2507941
• NM_002207.3:c.609C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002207.3(ITGA9):​c.609C>T​(p.Thr203Thr) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.91
• Publications: 9 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 -21 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 VariationId is 402988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002207.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA9	NM_002207.3	MANE Select	c.609C>T	p.Thr203Thr	synonymous	Exon 5 of 28	NP_002198.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA9	ENST00000264741.10	TSL:1 MANE Select	c.609C>T	p.Thr203Thr	synonymous	Exon 5 of 28	ENSP00000264741.5
	ITGA9	ENST00000422441.5	TSL:1	c.609C>T	p.Thr203Thr	synonymous	Exon 5 of 16	ENSP00000397258.1

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

GnomAD2 exomes AF: 0.0491 AC: 12312 AN: 250738 AF XY: 0.0504

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 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

African (AFR) AF: 0.0135 AC: 452 AN: 33442

American (AMR) AF: 0.0490 AC: 2189 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0374 AC: 976 AN: 26104

East Asian (EAS) AF: 0.0731 AC: 2899 AN: 39682

South Asian (SAS) AF: 0.0522 AC: 4501 AN: 86170

European-Finnish (FIN) AF: 0.0265 AC: 1414 AN: 53410

Middle Eastern (MID) AF: 0.0718 AC: 414 AN: 5764

European-Non Finnish (NFE) AF: 0.0589 AC: 65355 AN: 1109798

Other (OTH) AF: 0.0596 AC: 3597 AN: 60306

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

African (AFR) AF: 0.0149 AC: 618 AN: 41566

American (AMR) AF: 0.0699 AC: 1070 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3470

East Asian (EAS) AF: 0.0706 AC: 365 AN: 5172

South Asian (SAS) AF: 0.0466 AC: 225 AN: 4828

European-Finnish (FIN) AF: 0.0257 AC: 273 AN: 10614

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0590 AC: 4012 AN: 68020

Other (OTH) AF: 0.0605 AC: 128 AN: 2116

Alfa AF: 0.0544 Hom.: 847

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:2

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: 5% 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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.5
DANN	Benign	0.66
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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