chr17-50072022-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002204.4(ITGA3):c.996C>T(p.Phe332Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,613,448 control chromosomes in the GnomAD database, including 16,649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3528 hom., cov: 31)

Exomes 𝑓: 0.11 ( 13121 hom. )

Consequence

ITGA3
NM_002204.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.999

Publications

22 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 17-50072022-C-T is Benign according to our data. Variant chr17-50072022-C-T is described in ClinVar as Benign. ClinVar VariationId is 1271410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.999 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002204.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA3	NM_002204.4	MANE Select	c.996C>T	p.Phe332Phe	synonymous	Exon 7 of 26	NP_002195.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ITGA3	ENST00000320031.13	TSL:1 MANE Select	c.996C>T	p.Phe332Phe	synonymous	Exon 7 of 26	ENSP00000315190.8
ITGA3	ENST00000007722.11	TSL:5	c.996C>T	p.Phe332Phe	synonymous	Exon 7 of 25	ENSP00000007722.7
ITGA3	ENST00000505306.5	TSL:2	n.1368C>T		non_coding_transcript_exon	Exon 7 of 24

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28077

AN:

151844

Hom.:

3511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.0813

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.0975

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0889

Gnomad OTH

AF:

0.165

GnomAD2 exomes

AF:

0.167

AC:

41908

AN:

250798

AF XY:

0.162

show subpopulations

Gnomad AFR exome

AF:

0.344

Gnomad AMR exome

AF:

0.250

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.320

Gnomad FIN exome

AF:

0.0991

Gnomad NFE exome

AF:

0.0927

Gnomad OTH exome

AF:

0.141

GnomAD4 exome

AF:

0.114

AC:

166596

AN:

1461486

Hom.:

13121

Cov.:

AF XY:

0.116

AC XY:

84575

AN XY:

727078

show subpopulations

African (AFR)

AF:

0.342

AC:

11464

AN:

33476

American (AMR)

AF:

0.246

AC:

11012

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

3002

AN:

26116

East Asian (EAS)

AF:

0.316

AC:

12552

AN:

39696

South Asian (SAS)

AF:

0.234

AC:

20216

AN:

86242

European-Finnish (FIN)

AF:

0.0970

AC:

5179

AN:

53384

Middle Eastern (MID)

AF:

0.118

AC:

679

AN:

5760

European-Non Finnish (NFE)

AF:

0.0850

AC:

94493

AN:

1111734

Other (OTH)

AF:

0.132

AC:

7999

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

7058

14116

21175

28233

35291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3836

7672

11508

15344

19180

<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:

0.185

AC:

28157

AN:

151962

Hom.:

3528

Cov.:

AF XY:

0.189

AC XY:

14048

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.337

AC:

13950

AN:

41428

American (AMR)

AF:

0.224

AC:

3420

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

410

AN:

3470

East Asian (EAS)

AF:

0.316

AC:

1617

AN:

5124

South Asian (SAS)

AF:

0.254

AC:

1221

AN:

4816

European-Finnish (FIN)

AF:

0.0975

AC:

1032

AN:

10586

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0889

AC:

6041

AN:

67956

Other (OTH)

AF:

0.169

AC:

357

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1062

2123

3185

4246

5308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.125

Hom.:

2715

Bravo

AF:

0.199

Asia WGS

AF:

0.292

AC:

1016

AN:

3478

EpiCase

AF:

0.0936

EpiControl

AF:

0.0961

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.8

(source)

DANN

Benign

0.63

PhyloP100

-1.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over