chr3-37477054-T-A

Variant names:

• chr3-37477054-T-A
• rs189897
• NM_002207.3:c.420+3594T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002207.3(ITGA9):​c.420+3594T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,228 control chromosomes in the GnomAD database, including 1,717 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1717 hom., cov: 32)
• Consequence: ITGA9 NM_002207.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86
• Publications: 22 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA9	NM_002207.3	c.420+3594T>A		intron_variant	Intron 3 of 27	ENST00000264741.10	NP_002198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA9	ENST00000264741.10	c.420+3594T>A		intron_variant	Intron 3 of 27	1	NM_002207.3	ENSP00000264741.5
ITGA9	ENST00000422441.5	c.420+3594T>A		intron_variant	Intron 3 of 15	1		ENSP00000397258.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20475 AN: 152110 Hom.: 1715 Cov.: 32

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0668

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.147

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.135 AC: 20490 AN: 152228 Hom.: 1717 Cov.: 32 AF XY: 0.132 AC XY: 9850 AN XY: 74402

African (AFR) AF: 0.0429 AC: 1783 AN: 41548

American (AMR) AF: 0.168 AC: 2563 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3472

East Asian (EAS) AF: 0.0671 AC: 348 AN: 5186

South Asian (SAS) AF: 0.120 AC: 576 AN: 4814

European-Finnish (FIN) AF: 0.153 AC: 1617 AN: 10588

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.183 AC: 12438 AN: 68004

Other (OTH) AF: 0.144 AC: 305 AN: 2116

Alfa AF: 0.169 Hom.: 1291

Bravo AF: 0.131

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.023
DANN	Benign	0.37
PhyloP100		-2.9
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: rs189897; hg19: chr3-37518545;