Genetic Variant ITGA9:p.Thr203Thr (chr3-37494565-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002207.3(ITGA9):c.609C>T(p.Thr203Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 1,611,664 control chromosomes in the GnomAD database, including 2,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 205 hom., cov: 33)

Exomes 𝑓: 0.056 ( 2527 hom. )

Consequence

ITGA9
NM_002207.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.91

Publications

9 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 3-37494565-C-T is Benign according to our data. Variant chr3-37494565-C-T is described in ClinVar as Benign. ClinVar VariationId is 402988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.91 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA9	NM_002207.3 link	c.609C>T	p.Thr203Thr	synonymous_variant	Exon 5 of 28	ENST00000264741.10	NP_002198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA9	ENST00000264741.10 link	c.609C>T	p.Thr203Thr	synonymous_variant	Exon 5 of 28	1	NM_002207.3	ENSP00000264741.5
ITGA9	ENST00000422441.5 link	c.609C>T	p.Thr203Thr	synonymous_variant	Exon 5 of 16	1		ENSP00000397258.1

Frequencies

GnomAD3 genomes

AF:

0.0455

AC:

6922

AN:

152172

Hom.:

206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0149

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.0701

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.0706

Gnomad SAS

AF:

0.0466

Gnomad FIN

AF:

0.0257

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0590

Gnomad OTH

AF:

0.0573

GnomAD2 exomes

AF:

0.0491

AC:

12312

AN:

250738

AF XY:

0.0504

show subpopulations

Gnomad AFR exome

AF:

0.0147

Gnomad AMR exome

AF:

0.0470

Gnomad ASJ exome

AF:

0.0369

Gnomad EAS exome

AF:

0.0641

Gnomad FIN exome

AF:

0.0259

Gnomad NFE exome

AF:

0.0569

Gnomad OTH exome

AF:

0.0557

GnomAD4 exome

AF:

0.0560

AC:

81797

AN:

1459374

Hom.:

2527

Cov.:

AF XY:

0.0557

AC XY:

40454

AN XY:

726126

show subpopulations

African (AFR)

AF:

0.0135

AC:

452

AN:

33442

American (AMR)

AF:

0.0490

AC:

2189

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0374

AC:

976

AN:

26104

East Asian (EAS)

AF:

0.0731

AC:

2899

AN:

39682

South Asian (SAS)

AF:

0.0522

AC:

4501

AN:

86170

European-Finnish (FIN)

AF:

0.0265

AC:

1414

AN:

53410

Middle Eastern (MID)

AF:

0.0718

AC:

414

AN:

5764

European-Non Finnish (NFE)

AF:

0.0589

AC:

65355

AN:

1109798

Other (OTH)

AF:

0.0596

AC:

3597

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

3742

7484

11225

14967

18709

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2468

4936

7404

9872

12340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0455

AC:

6926

AN:

152290

Hom.:

205

Cov.:

AF XY:

0.0454

AC XY:

3382

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0149

AC:

618

AN:

41566

American (AMR)

AF:

0.0699

AC:

1070

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0343

AC:

119

AN:

3470

East Asian (EAS)

AF:

0.0706

AC:

365

AN:

5172

South Asian (SAS)

AF:

0.0466

AC:

225

AN:

4828

European-Finnish (FIN)

AF:

0.0257

AC:

273

AN:

10614

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0590

AC:

4012

AN:

68020

Other (OTH)

AF:

0.0605

AC:

128

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

358

716

1073

1431

1789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0544

Hom.:

847

Bravo

AF:

0.0476

Asia WGS

AF:

0.0550

AC:

189

AN:

3478

EpiCase

AF:

0.0587

EpiControl

AF:

0.0637

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 5% of total chromosomes in ExAC

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

-0.57

CADD

Benign

5.5

(source)

DANN

Benign

0.66

PhyloP100

-2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over