rs2230392

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002204.4(ITGA3):c.2155G>A(p.Ala719Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,610,498 control chromosomes in the GnomAD database, including 11,729 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.095 ( 1082 hom., cov: 32)

Exomes 𝑓: 0.10 ( 10647 hom. )

Consequence

ITGA3
NM_002204.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.53

Publications

29 publications found

Variant links:

Genes affected

ITGA3 (HGNC:6139): (integrin subunit alpha 3) The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function as cell surface adhesion molecules. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 3 subunit. This subunit joins with a beta 1 subunit to form an integrin that interacts with extracellular matrix proteins including members of the laminin family. Expression of this gene may be correlated with breast cancer metastasis. [provided by RefSeq, Oct 2015]

ITGA3 Gene-Disease associations (from GenCC):

epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, Ambry Genetics, Orphanet, G2P

ITGA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030632317).

BP6

Variant 17-50078061-G-A is Benign according to our data. Variant chr17-50078061-G-A is described in ClinVar as Benign. ClinVar VariationId is 1237071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA3	NM_002204.4 link	c.2155G>A	p.Ala719Thr	missense_variant	Exon 17 of 26	ENST00000320031.13	NP_002195.1	P26006-2A0A140VJM0
ITGA3	XM_005257308.3 link	c.1750G>A	p.Ala584Thr	missense_variant	Exon 15 of 24		XP_005257365.1
ITGA3	XM_047435922.1 link	c.2196G>A	p.Ser732Ser	synonymous_variant	Exon 17 of 18		XP_047291878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA3	ENST00000320031.13 link	c.2155G>A	p.Ala719Thr	missense_variant	Exon 17 of 26	1	NM_002204.4	ENSP00000315190.8		P26006-2

Frequencies

GnomAD3 genomes

AF:

0.0952

AC:

14477

AN:

152042

Hom.:

1080

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0235

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.0990

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0874

Gnomad OTH

AF:

0.111

GnomAD2 exomes

AF:

0.143

AC:

35811

AN:

250822

AF XY:

0.144

show subpopulations

Gnomad AFR exome

AF:

0.0209

Gnomad AMR exome

AF:

0.236

Gnomad ASJ exome

AF:

0.0969

Gnomad EAS exome

AF:

0.324

Gnomad FIN exome

AF:

0.0999

Gnomad NFE exome

AF:

0.0911

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.104

AC:

151264

AN:

1458338

Hom.:

10647

Cov.:

AF XY:

0.107

AC XY:

77698

AN XY:

724896

show subpopulations

African (AFR)

AF:

0.0183

AC:

613

AN:

33444

American (AMR)

AF:

0.230

AC:

10259

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.0998

AC:

2602

AN:

26084

East Asian (EAS)

AF:

0.318

AC:

12597

AN:

39586

South Asian (SAS)

AF:

0.233

AC:

20011

AN:

85990

European-Finnish (FIN)

AF:

0.0981

AC:

5234

AN:

53354

Middle Eastern (MID)

AF:

0.106

AC:

610

AN:

5754

European-Non Finnish (NFE)

AF:

0.0835

AC:

92660

AN:

1109364

Other (OTH)

AF:

0.111

AC:

6678

AN:

60156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

6213

12425

18638

24850

31063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3618

7236

10854

14472

18090

<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:

0.0952

AC:

14491

AN:

152160

Hom.:

1082

Cov.:

AF XY:

0.103

AC XY:

7652

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0235

AC:

975

AN:

41518

American (AMR)

AF:

0.193

AC:

2949

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

365

AN:

3472

East Asian (EAS)

AF:

0.318

AC:

1636

AN:

5144

South Asian (SAS)

AF:

0.253

AC:

1222

AN:

4822

European-Finnish (FIN)

AF:

0.0990

AC:

1049

AN:

10594

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0874

AC:

5944

AN:

68006

Other (OTH)

AF:

0.116

AC:

245

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

642

1283

1925

2566

3208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<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:

0.0982

Hom.:

2449

Bravo

AF:

0.0966

TwinsUK

AF:

0.0885

AC:

328

ALSPAC

AF:

0.0807

AC:

311

ESP6500AA

AF:

0.0225

AC:

ESP6500EA

AF:

0.0888

AC:

764

ExAC

AF:

0.138

AC:

16782

Asia WGS

AF:

0.275

AC:

955

AN:

3478

EpiCase

AF:

0.0914

EpiControl

AF:

0.0936

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

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

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

T;.

Eigen

Benign

-0.076

Eigen_PC

Benign

-0.0095

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.75

T;T

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

L;L

PhyloP100

1.5

PrimateAI

Benign

0.35

PROVEAN

Benign

0.27

N;N

REVEL

Benign

0.010

Sift

Benign

0.36

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.20

B;B

Vest4

0.026

MPC

0.36

ClinPred

0.0099

GERP RS

3.2

Varity_R

0.050

gMVP

0.39

Mutation Taster

=99/1

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