Genetic Variant ITGA3:n.661C>T (chr17-50089616-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000514834.1(ITGA3):n.661C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 234,606 control chromosomes in the GnomAD database, including 1,764 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 0.089 ( 1006 hom., cov: 31)

Exomes 𝑓: 0.098 ( 758 hom. )

Consequence

ITGA3
ENST00000514834.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.20

Publications

4 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA3	NM_002204.4 link	c.*538C>T		3_prime_UTR_variant	Exon 26 of 26	ENST00000320031.13	NP_002195.1	P26006-2A0A140VJM0
ITGA3	XM_005257308.3 link	c.*538C>T		3_prime_UTR_variant	Exon 24 of 24		XP_005257365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA3	ENST00000320031.13 link	c.*538C>T		3_prime_UTR_variant	Exon 26 of 26	1	NM_002204.4	ENSP00000315190.8		P26006-2

Frequencies

GnomAD3 genomes

AF:

0.0892

AC:

13564

AN:

151990

Hom.:

1004

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.0939

Gnomad EAS

AF:

0.323

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.0905

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0765

Gnomad OTH

AF:

0.106

GnomAD4 exome

AF:

0.0983

AC:

8107

AN:

82498

Hom.:

758

Cov.:

AF XY:

0.102

AC XY:

4319

AN XY:

42542

show subpopulations

African (AFR)

AF:

0.0197

AC:

AN:

3962

American (AMR)

AF:

0.178

AC:

877

AN:

4940

Ashkenazi Jewish (ASJ)

AF:

0.0831

AC:

230

AN:

2768

East Asian (EAS)

AF:

0.312

AC:

1852

AN:

5940

South Asian (SAS)

AF:

0.194

AC:

1088

AN:

5620

European-Finnish (FIN)

AF:

0.0751

AC:

283

AN:

3766

Middle Eastern (MID)

AF:

0.0684

AC:

AN:

380

European-Non Finnish (NFE)

AF:

0.0640

AC:

3213

AN:

50202

Other (OTH)

AF:

0.0935

AC:

460

AN:

4920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

340

680

1019

1359

1699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.0893

AC:

13580

AN:

152108

Hom.:

1006

Cov.:

AF XY:

0.0964

AC XY:

7169

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0254

AC:

1056

AN:

41524

American (AMR)

AF:

0.188

AC:

2863

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0939

AC:

326

AN:

3470

East Asian (EAS)

AF:

0.323

AC:

1656

AN:

5126

South Asian (SAS)

AF:

0.245

AC:

1181

AN:

4812

European-Finnish (FIN)

AF:

0.0905

AC:

958

AN:

10588

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0765

AC:

5203

AN:

68004

Other (OTH)

AF:

0.111

AC:

234

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

583

1165

1748

2330

2913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.0821

Hom.:

851

Bravo

AF:

0.0911

Asia WGS

AF:

0.276

AC:

958

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over