dbSNP rs16948627: ITGA3:c.207-645C>A (chr17-50063432-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002204.4(ITGA3):c.207-645C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0993 in 152,496 control chromosomes in the GnomAD database, including 1,211 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 0.099 ( 1210 hom., cov: 32)

Exomes 𝑓: 0.086 ( 1 hom. )

Consequence

ITGA3
NM_002204.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0380

Publications

3 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=-0.72).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 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.207-645C>A		intron	N/A	NP_002195.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ITGA3	ENST00000320031.13	TSL:1 MANE Select	c.207-645C>A	intron	N/A	ENSP00000315190.8
ITGA3	ENST00000007722.11	TSL:5	c.207-645C>A	intron	N/A	ENSP00000007722.7
ITGA3	ENST00000505306.5	TSL:2	n.579-645C>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0992

AC:

15092

AN:

152100

Hom.:

1204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0241

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.322

Gnomad SAS

AF:

0.253

Gnomad FIN

AF:

0.0993

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0887

Gnomad OTH

AF:

0.112

GnomAD4 exome

AF:

0.0863

AC:

AN:

278

Hom.:

AF XY:

0.0714

AC XY:

AN XY:

168

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.167

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0861

AC:

AN:

244

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0993

AC:

15112

AN:

152218

Hom.:

1210

Cov.:

AF XY:

0.107

AC XY:

7961

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0240

AC:

999

AN:

41556

American (AMR)

AF:

0.224

AC:

3427

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

367

AN:

3468

East Asian (EAS)

AF:

0.322

AC:

1665

AN:

5164

South Asian (SAS)

AF:

0.251

AC:

1214

AN:

4830

European-Finnish (FIN)

AF:

0.0993

AC:

1052

AN:

10598

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0888

AC:

6036

AN:

68004

Other (OTH)

AF:

0.117

AC:

247

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

665

1330

1996

2661

3326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.0446

Hom.:

Bravo

AF:

0.106

Asia WGS

AF:

0.274

AC:

952

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.8

(source)

DANN

Benign

0.84

PhyloP100

-0.038

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over