3-37732734-A-G

Variant names:

• chr3-37732734-A-G
• rs142726080
• NM_002207.3:c.2090A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002207.3(ITGA9):​c.2090A>G​(p.Glu697Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00176 in 1,610,140 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0091 (29 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (27 hom.)
• Consequence: ITGA9 NM_002207.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.73
• Publications: 3 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]

ITGA9-AS1 (HGNC:49668): (ITGA9 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006268263).
• BP6: Variant 3-37732734-A-G is Benign according to our data. Variant chr3-37732734-A-G is described in ClinVar as Benign. ClinVar VariationId is 702568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00914 (1391/152190) while in subpopulation AFR AF = 0.0312 (1297/41516). AF 95% confidence interval is 0.0298. There are 29 homozygotes in GnomAd4. There are 647 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 gene

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.2090A>G	p.Glu697Gly	missense	Exon 19 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.2090A>G	p.Glu697Gly	missense	Exon 19 of 28	ENSP00000264741.5	Q13797
	ITGA9	ENST00000921363.1		c.2090A>G	p.Glu697Gly	missense	Exon 19 of 28	ENSP00000591422.1
	ITGA9	ENST00000944256.1		c.2087A>G	p.Glu696Gly	missense	Exon 19 of 28	ENSP00000614315.1

Frequencies

GnomAD3 genomes AF: 0.00915 AC: 1392 AN: 152072 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00243 AC: 591 AN: 243420 AF XY: 0.00191

Gnomad AFR exome AF: 0.0319

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000199

Gnomad OTH exome AF: 0.00237

GnomAD4 exome AF: 0.000988 AC: 1441 AN: 1457950 Hom.: 27 Cov.: 31 AF XY: 0.000853 AC XY: 618 AN XY: 724570

African (AFR) AF: 0.0334 AC: 1118 AN: 33450

American (AMR) AF: 0.00230 AC: 102 AN: 44284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5762

European-Non Finnish (NFE) AF: 0.0000900 AC: 100 AN: 1110916

Other (OTH) AF: 0.00179 AC: 108 AN: 60276

GnomAD4 genome AF: 0.00914 AC: 1391 AN: 152190 Hom.: 29 Cov.: 32 AF XY: 0.00870 AC XY: 647 AN XY: 74388

African (AFR) AF: 0.0312 AC: 1297 AN: 41516

American (AMR) AF: 0.00458 AC: 70 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68012

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00373 Hom.: 19

Bravo AF: 0.0109

ESP6500AA AF: 0.0327 AC: 144

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00290 AC: 352

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.017
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.7
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.084
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.10	T
Polyphen		0.020	B
Vest4		0.23
MVP		0.48
MPC		0.24
ClinPred		0.041	T
GERP RS		5.7
Varity_R		0.25
gMVP		0.58
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs142726080; hg19: chr3-37774225;