Genetic Variant ITGB3:c.80-7123G>T (chr17-47267296-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000212.3(ITGB3):c.80-7123G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,992 control chromosomes in the GnomAD database, including 9,386 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 0.34 ( 9386 hom., cov: 32)

Consequence

ITGB3
NM_000212.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.135

Publications

3 publications found

Variant links:

Genes affected

ITGB3 (HGNC:6156): (integrin subunit beta 3) The ITGB3 protein product is the integrin beta chain beta 3. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain. A given chain may combine with multiple partners resulting in different integrins. Integrin beta 3 is found along with the alpha IIb chain in platelets. Integrins are known to participate in cell adhesion as well as cell-surface mediated signalling. [provided by RefSeq, Jul 2008]

ITGB3 Gene-Disease associations (from GenCC):

Glanzmann thrombasthenia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Glanzmann thrombasthenia 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
bleeding disorder, platelet-type, 24
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
platelet-type bleeding disorder 16
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
autosomal dominant macrothrombocytopenia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Glanzmann's thrombasthenia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ITGB3 links:

ENSG00000259753 (HGNC:):

ENSG00000259753 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB3	NM_000212.3 link	c.80-7123G>T		intron_variant	Intron 1 of 14	ENST00000559488.7	NP_000203.2	P05106-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITGB3	ENST00000559488.7 link	c.80-7123G>T	intron_variant	Intron 1 of 14	1	NM_000212.3	ENSP00000452786.2	P05106-1
ITGB3	ENST00000571680.1 link	c.80-7123G>T	intron_variant	Intron 1 of 8	1		ENSP00000461626.1	I3L4X8
ENSG00000259753	ENST00000560629.1 link	n.44-7123G>T	intron_variant	Intron 1 of 17	2		ENSP00000456711.2	H3BM21
ITGB3	ENST00000696963.1 link	c.80-7123G>T	intron_variant	Intron 1 of 13			ENSP00000513002.1	P05106-2

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52364

AN:

151872

Hom.:

9373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.406

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.515

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.318

Gnomad NFE

AF:

0.307

Gnomad OTH

AF:

0.351

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.345

AC:

52419

AN:

151992

Hom.:

9386

Cov.:

AF XY:

0.346

AC XY:

25704

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.407

AC:

16839

AN:

41418

American (AMR)

AF:

0.313

AC:

4775

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

1095

AN:

3472

East Asian (EAS)

AF:

0.516

AC:

2668

AN:

5168

South Asian (SAS)

AF:

0.407

AC:

1958

AN:

4814

European-Finnish (FIN)

AF:

0.295

AC:

3119

AN:

10568

Middle Eastern (MID)

AF:

0.308

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.307

AC:

20846

AN:

67958

Other (OTH)

AF:

0.347

AC:

733

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1741

3482

5223

6964

8705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.320

Hom.:

2914

Bravo

AF:

0.345

Asia WGS

AF:

0.466

AC:

1621

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.0

(source)

DANN

Benign

0.37

PhyloP100

-0.14

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over