rs373225022

Variant names:

• chr3-37741744-G-A
• rs373225022
• NM_002207.3:c.2249G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-37741744-G-A
• chr3-37741744-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002207.3(ITGA9):​c.2249G>A​(p.Arg750His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,613,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: ITGA9 NM_002207.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.91
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08167276).

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.2249G>A	p.Arg750His	missense	Exon 21 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.2249G>A	p.Arg750His	missense	Exon 21 of 28	ENSP00000264741.5	Q13797
	ITGA9	ENST00000921363.1		c.2249G>A	p.Arg750His	missense	Exon 21 of 28	ENSP00000591422.1
	ITGA9	ENST00000944256.1		c.2246G>A	p.Arg749His	missense	Exon 21 of 28	ENSP00000614315.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152236 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000560 AC: 14 AN: 250076 AF XY: 0.0000518

Gnomad AFR exome AF: 0.0000620

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000431 AC: 63 AN: 1461260 Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28 AN XY: 726856

African (AFR) AF: 0.0000598 AC: 2 AN: 33472

American (AMR) AF: 0.000157 AC: 7 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000468 AC: 52 AN: 1111742

Other (OTH) AF: 0.0000166 AC: 1 AN: 60366

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.000850 AC: 13 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68042

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.000132

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.058
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.37	N
PhyloP100		2.9
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.052
Sift	Benign	0.059	T
Sift4G	Benign	0.24	T
Polyphen		0.014	B
Vest4		0.17
MVP		0.44
MPC		0.25
ClinPred		0.054	T
GERP RS		5.2
Varity_R		0.049
gMVP		0.32
Mutation Taster		=86/14	polymorphism

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: rs373225022; hg19: chr3-37783235;