3-37506010-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_002207.3(ITGA9):c.753G>A(p.Val251=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00124 in 1,606,260 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (17 hom.)
• Consequence: ITGA9 NM_002207.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.68

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 3-37506010-G-A is Benign according to our data. Variant chr3-37506010-G-A is described in ClinVar as [Benign]. Clinvar id is 697425.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00645 (981/152150) while in subpopulation AFR AF= 0.0226 (939/41502). AF 95% confidence interval is 0.0214. There are 9 homozygotes in gnomad4. There are 471 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA9	NM_002207.3	c.753G>A	p.Val251=	synonymous_variant	7/28	ENST00000264741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA9	ENST00000264741.10	c.753G>A	p.Val251=	synonymous_variant	7/28	1	NM_002207.3	P1
ITGA9	ENST00000422441.5	c.753G>A	p.Val251=	synonymous_variant	7/16	1

Frequencies

GnomAD3 genomes AF: 0.00643 AC: 978 AN: 152032 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

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: 0.0000441

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.00159 AC: 380 AN: 238408 Hom.: 8 AF XY: 0.00120 AC XY: 154 AN XY: 128154

Gnomad AFR exome AF: 0.0226

Gnomad AMR exome AF: 0.000842

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000106

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000278

Gnomad OTH exome AF: 0.000854

GnomAD4 exome AF: 0.000690 AC: 1003 AN: 1454110 Hom.: 17 Cov.: 31 AF XY: 0.000616 AC XY: 445 AN XY: 722264

Gnomad4 AFR exome AF: 0.0241

Gnomad4 AMR exome AF: 0.000984

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000190

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.00186

GnomAD4 genome AF: 0.00645 AC: 981 AN: 152150 Hom.: 9 Cov.: 32 AF XY: 0.00633 AC XY: 471 AN XY: 74390

Gnomad4 AFR AF: 0.0226

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00224 Hom.: 4

Bravo AF: 0.00740

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	4.1
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs145968481; hg19: chr3-37547501;