rs267561

Variant names:

• chr3-37533460-G-A
• rs267561
• NM_002207.3:c.1520G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-37533460-G-A
• chr3-37533460-G-C
• chr3-37533460-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002207.3(ITGA9):​c.1520G>A​(p.Gly507Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,613,482 control chromosomes in the GnomAD database, including 274,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23851 hom., cov: 32)
  • Exomes 𝑓: 0.58 (250743 hom.)
• Consequence: ITGA9 NM_002207.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 7.88
• Publications: 41 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.7952218E-6).
• BP6: Variant 3-37533460-G-A is Benign according to our data. Variant chr3-37533460-G-A is described in ClinVar as Benign. ClinVar VariationId is 402989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA9	NM_002207.3	MANE Select	c.1520G>A	p.Gly507Glu	missense	Exon 14 of 28	NP_002198.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA9	ENST00000264741.10	TSL:1 MANE Select	c.1520G>A	p.Gly507Glu	missense	Exon 14 of 28	ENSP00000264741.5	Q13797
	ITGA9	ENST00000422441.5	TSL:1	c.1520G>A	p.Gly507Glu	missense	Exon 14 of 16	ENSP00000397258.1	E9PDS3
	ITGA9	ENST00000921363.1		c.1520G>A	p.Gly507Glu	missense	Exon 14 of 28	ENSP00000591422.1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83873 AN: 151892 Hom.: 23825 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.539

GnomAD2 exomes AF: 0.583 AC: 146132 AN: 250708 AF XY: 0.570

Gnomad AFR exome AF: 0.467

Gnomad AMR exome AF: 0.740

Gnomad ASJ exome AF: 0.499

Gnomad EAS exome AF: 0.813

Gnomad FIN exome AF: 0.569

Gnomad NFE exome AF: 0.575

Gnomad OTH exome AF: 0.563

GnomAD4 exome AF: 0.581 AC: 849080 AN: 1461472 Hom.: 250743 Cov.: 50 AF XY: 0.574 AC XY: 417278 AN XY: 727020

African (AFR) AF: 0.460 AC: 15387 AN: 33474

American (AMR) AF: 0.724 AC: 32376 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 12966 AN: 26134

East Asian (EAS) AF: 0.793 AC: 31472 AN: 39688

South Asian (SAS) AF: 0.407 AC: 35079 AN: 86228

European-Finnish (FIN) AF: 0.566 AC: 30199 AN: 53352

Middle Eastern (MID) AF: 0.421 AC: 2427 AN: 5766

European-Non Finnish (NFE) AF: 0.589 AC: 654906 AN: 1111756

Other (OTH) AF: 0.568 AC: 34268 AN: 60380

GnomAD4 genome AF: 0.552 AC: 83941 AN: 152010 Hom.: 23851 Cov.: 32 AF XY: 0.550 AC XY: 40868 AN XY: 74284

African (AFR) AF: 0.463 AC: 19182 AN: 41452

American (AMR) AF: 0.635 AC: 9698 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1731 AN: 3470

East Asian (EAS) AF: 0.812 AC: 4178 AN: 5144

South Asian (SAS) AF: 0.406 AC: 1951 AN: 4806

European-Finnish (FIN) AF: 0.572 AC: 6053 AN: 10580

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39330 AN: 67966

Other (OTH) AF: 0.539 AC: 1137 AN: 2108

Alfa AF: 0.571 Hom.: 85415

Bravo AF: 0.562

TwinsUK AF: 0.595 AC: 2205

ALSPAC AF: 0.587 AC: 2263

ESP6500AA AF: 0.471 AC: 2077

ESP6500EA AF: 0.580 AC: 4991

ExAC AF: 0.571 AC: 69371

Asia WGS AF: 0.579 AC: 2016 AN: 3478

EpiCase AF: 0.562

EpiControl AF: 0.569

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	ITGA9-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0000018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.27
Sift	Benign	0.031	D
Sift4G	Uncertain	0.010	D
Polyphen		0.53	P
Vest4		0.31
MPC		0.40
ClinPred		0.054	T
GERP RS		5.9
Varity_R		0.53
gMVP		0.73
Mutation Taster		=74/26	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs267561; hg19: chr3-37574951; COSMIC: COSV53237444;