NM_002207.3:c.294C>A

Variant names:

• chr3-37471115-C-A
• rs17036383
• NM_002207.3:c.294C>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002207.3(ITGA9):​c.294C>A​(p.Thr98Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00522 in 1,613,906 control chromosomes in the GnomAD database, including 274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (146 hom., cov: 31)
  • Exomes 𝑓: 0.0032 (128 hom.)
• Consequence: ITGA9 NM_002207.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.50
• Publications: 1 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 3-37471115-C-A is Benign according to our data. Variant chr3-37471115-C-A is described in ClinVar as Benign. ClinVar VariationId is 702082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.5 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0795 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.294C>A	p.Thr98Thr	synonymous	Exon 2 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.294C>A	p.Thr98Thr	synonymous	Exon 2 of 28	ENSP00000264741.5	Q13797
	ITGA9	ENST00000422441.5	TSL:1	c.294C>A	p.Thr98Thr	synonymous	Exon 2 of 16	ENSP00000397258.1	E9PDS3
	ITGA9	ENST00000921363.1		c.294C>A	p.Thr98Thr	synonymous	Exon 2 of 28	ENSP00000591422.1

Frequencies

GnomAD3 genomes AF: 0.0248 AC: 3771 AN: 151996 Hom.: 145 Cov.: 31

Gnomad AFR AF: 0.0821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.00736 AC: 1852 AN: 251470 AF XY: 0.00578

Gnomad AFR exome AF: 0.0813

Gnomad AMR exome AF: 0.00642

Gnomad ASJ exome AF: 0.0169

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000826

Gnomad OTH exome AF: 0.00701

GnomAD4 exome AF: 0.00318 AC: 4653 AN: 1461792 Hom.: 128 Cov.: 31 AF XY: 0.00286 AC XY: 2082 AN XY: 727194

African (AFR) AF: 0.0839 AC: 2807 AN: 33468

American (AMR) AF: 0.00707 AC: 316 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0174 AC: 456 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00919 AC: 53 AN: 5768

European-Non Finnish (NFE) AF: 0.000476 AC: 529 AN: 1111958

Other (OTH) AF: 0.00793 AC: 479 AN: 60386

GnomAD4 genome AF: 0.0248 AC: 3769 AN: 152114 Hom.: 146 Cov.: 31 AF XY: 0.0236 AC XY: 1757 AN XY: 74350

African (AFR) AF: 0.0818 AC: 3394 AN: 41474

American (AMR) AF: 0.0139 AC: 213 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000625 AC: 3 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68014

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0102 Hom.: 36

Bravo AF: 0.0292

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.00113

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ITGA9-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	2.8
DANN	Benign	0.69
PhyloP100		-1.5
Mutation Taster		=100/0	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: rs17036383; hg19: chr3-37512606;