chr3-37471115-C-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id is 702082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-37471115-C-A is described in Lovd as [Benign].
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA9	NM_002207.3	c.294C>A	p.Thr98Thr	synonymous_variant	Exon 2 of 28	ENST00000264741.10	NP_002198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA9	ENST00000264741.10	c.294C>A	p.Thr98Thr	synonymous_variant	Exon 2 of 28	1	NM_002207.3	ENSP00000264741.5
ITGA9	ENST00000422441.5	c.294C>A	p.Thr98Thr	synonymous_variant	Exon 2 of 16	1		ENSP00000397258.1

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

GnomAD3 exomes AF: 0.00736 AC: 1852 AN: 251470 Hom.: 58 AF XY: 0.00578 AC XY: 785 AN XY: 135914

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 SAS exome AF: 0.0000653

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

Gnomad4 AFR exome AF: 0.0839

Gnomad4 AMR exome AF: 0.00707

Gnomad4 ASJ exome AF: 0.0174

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000476

Gnomad4 OTH exome AF: 0.00793

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

Gnomad4 AFR AF: 0.0818

Gnomad4 AMR AF: 0.0139

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000625

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.00942 Hom.: 19

Bravo AF: 0.0292

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

ITGA9-related disorder Benign:1

Feb 18, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	2.8
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs17036383; hg19: chr3-37512606;