Genetic Variant NM_000212.3:c.80-8072C>T (chr17-47266347-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 NM_000212.3(ITGB3):c.80-8072C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,108 control chromosomes in the GnomAD database, including 5,571 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 0.26 ( 5571 hom., cov: 32)

Consequence

ITGB3
NM_000212.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.565

Publications

6 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB3	NM_000212.3 link	c.80-8072C>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.80-8072C>T	intron_variant	Intron 1 of 14	1	NM_000212.3	ENSP00000452786.2	P05106-1
ITGB3	ENST00000571680.1 link	c.80-8072C>T	intron_variant	Intron 1 of 8	1		ENSP00000461626.1	I3L4X8
ENSG00000259753	ENST00000560629.1 link	n.44-8072C>T	intron_variant	Intron 1 of 17	2		ENSP00000456711.2	H3BM21
ITGB3	ENST00000696963.1 link	c.80-8072C>T	intron_variant	Intron 1 of 13			ENSP00000513002.1	P05106-2

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40158

AN:

151990

Hom.:

5563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.323

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.253

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.262

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

GnomAD4 genome

AF:

0.264

AC:

40193

AN:

152108

Hom.:

5571

Cov.:

AF XY:

0.262

AC XY:

19462

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.323

AC:

13405

AN:

41476

American (AMR)

AF:

0.187

AC:

2857

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

713

AN:

3470

East Asian (EAS)

AF:

0.235

AC:

1217

AN:

5180

South Asian (SAS)

AF:

0.251

AC:

1208

AN:

4818

European-Finnish (FIN)

AF:

0.268

AC:

2834

AN:

10582

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.252

AC:

17146

AN:

67964

Other (OTH)

AF:

0.260

AC:

548

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1471

2942

4412

5883

7354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.262

Hom.:

928

Bravo

AF:

0.259

Asia WGS

AF:

0.280

AC:

975

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.66

PhyloP100

-0.56

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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