Genetic Variant ITGA9:c.2667+32G>A (chr3-37777549-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002207.3(ITGA9):c.2667+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 1,612,482 control chromosomes in the GnomAD database, including 1,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 102 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1232 hom. )

Consequence

ITGA9
NM_002207.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.362

Variant links:

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 links:

ITGA9-AS1 (HGNC:49668): (ITGA9 antisense RNA 1)

ITGA9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-37777549-G-A is Benign according to our data. Variant chr3-37777549-G-A is described in ClinVar as [Benign]. Clinvar id is 94048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-37777549-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0312 (4749/152248) while in subpopulation NFE AF= 0.0479 (3256/68020). AF 95% confidence interval is 0.0465. There are 102 homozygotes in gnomad4. There are 2252 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 102 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA9	NM_002207.3 link	c.2667+32G>A		intron_variant	Intron 24 of 27	ENST00000264741.10	NP_002198.2	Q13797Q8N6H6
ITGA9-AS1	NR_110531.1 link	n.257-23497C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA9	ENST00000264741.10 link	c.2667+32G>A		intron_variant	Intron 24 of 27	1	NM_002207.3	ENSP00000264741.5		Q13797

Frequencies

GnomAD3 genomes

AF:

0.0312

AC:

4747

AN:

152130

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.0705

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.0366

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0479

Gnomad OTH

AF:

0.0259

GnomAD3 exomes

AF:

0.0311

AC:

7820

AN:

251212

Hom.:

149

AF XY:

0.0316

AC XY:

4290

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.0161

Gnomad ASJ exome

AF:

0.0216

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0152

Gnomad FIN exome

AF:

0.0370

Gnomad NFE exome

AF:

0.0475

Gnomad OTH exome

AF:

0.0335

GnomAD4 exome

AF:

0.0386

AC:

56384

AN:

1460234

Hom.:

1232

Cov.:

AF XY:

0.0385

AC XY:

27993

AN XY:

726510

show subpopulations

Gnomad4 AFR exome

AF:

0.0107

Gnomad4 AMR exome

AF:

0.0169

Gnomad4 ASJ exome

AF:

0.0208

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0152

Gnomad4 FIN exome

AF:

0.0381

Gnomad4 NFE exome

AF:

0.0443

Gnomad4 OTH exome

AF:

0.0338

GnomAD4 genome

AF:

0.0312

AC:

4749

AN:

152248

Hom.:

102

Cov.:

AF XY:

0.0303

AC XY:

2252

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0118

Gnomad4 AMR

AF:

0.0231

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.0366

Gnomad4 NFE

AF:

0.0479

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.0307

Hom.:

Bravo

AF:

0.0290

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 02, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over