chr17-47307646-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP7BA1BP4

This summary comes from the ClinGen Evidence Repository: After a comprehensive literature search of the intronic variant NM_000212.3(ITGB3):c.2301+9C>T, no individuals with Glanzmann Thrombasthenia were reported with the variant. The variant has a high minor allele frequency of 0.4805 (11916/24800 alleles) in the African/African American population, which is higher than the ClinGen PD VCEP threshold (>0.0024), and therefore meets BA1. In silico predictor spliceAI revealed that the intronic mutation is not expected to impact splicing and a PhyloP score of -.336 shows that the nucleotide position is not highly conserved (BP4,BP7). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1, BP4 and BP7 (PD VCEP specifications version 2.1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA8623491/MONDO:0100326/011

Frequency

Genomes: 𝑓 0.46 ( 16187 hom., cov: 32)

Exomes 𝑓: 0.46 ( 158722 hom. )

Consequence

ITGB3
NM_000212.3 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:6

Conservation

PhyloP100: 0.370

Publications

38 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 links:

ENSG00000259753 (HGNC:):

ENSG00000259753 links:

EFCAB13-DT (HGNC:55338): (EFCAB13 divergent transcript)

EFCAB13-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

For more information check the summary or visit ClinGen Evidence Repository.

BP7

For more information check the summary or visit ClinGen Evidence Repository.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ITGB3	NM_000212.3 link	c.2301+9C>T	intron_variant	Intron 14 of 14	ENST00000559488.7	NP_000203.2	P05106-1
EFCAB13-DT	NR_110880.1 link	n.363-3864G>A	intron_variant	Intron 2 of 2
EFCAB13-DT	NR_110881.1 link	n.227-3864G>A	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7 link	c.2301+9C>T		intron_variant	Intron 14 of 14	1	NM_000212.3	ENSP00000452786.2		P05106-1
ENSG00000259753	ENST00000560629.1 link	n.2265+9C>T		intron_variant	Intron 14 of 17	2		ENSP00000456711.2		H3BM21

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69311

AN:

151934

Hom.:

16185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.480

Gnomad AMI

AF:

0.469

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.433

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.499

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.476

Gnomad OTH

AF:

0.439

GnomAD2 exomes

AF:

0.429

AC:

107220

AN:

249968

AF XY:

0.431

show subpopulations

Gnomad AFR exome

AF:

0.482

Gnomad AMR exome

AF:

0.354

Gnomad ASJ exome

AF:

0.419

Gnomad EAS exome

AF:

0.249

Gnomad FIN exome

AF:

0.494

Gnomad NFE exome

AF:

0.472

Gnomad OTH exome

AF:

0.432

GnomAD4 exome

AF:

0.463

AC:

676003

AN:

1460176

Hom.:

158722

Cov.:

AF XY:

0.461

AC XY:

335190

AN XY:

726390

show subpopulations

African (AFR)

AF:

0.475

AC:

15897

AN:

33440

American (AMR)

AF:

0.356

AC:

15872

AN:

44582

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

10915

AN:

26120

East Asian (EAS)

AF:

0.269

AC:

10683

AN:

39674

South Asian (SAS)

AF:

0.389

AC:

33552

AN:

86166

European-Finnish (FIN)

AF:

0.493

AC:

26318

AN:

53374

Middle Eastern (MID)

AF:

0.388

AC:

2239

AN:

5766

European-Non Finnish (NFE)

AF:

0.480

AC:

533193

AN:

1110700

Other (OTH)

AF:

0.453

AC:

27334

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

18626

37253

55879

74506

93132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15634

31268

46902

62536

78170

<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:

0.456

AC:

69347

AN:

152052

Hom.:

16187

Cov.:

AF XY:

0.453

AC XY:

33674

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.480

AC:

19888

AN:

41456

American (AMR)

AF:

0.374

AC:

5714

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

1501

AN:

3470

East Asian (EAS)

AF:

0.252

AC:

1305

AN:

5180

South Asian (SAS)

AF:

0.381

AC:

1835

AN:

4810

European-Finnish (FIN)

AF:

0.499

AC:

5277

AN:

10572

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.476

AC:

32356

AN:

67974

Other (OTH)

AF:

0.438

AC:

924

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1938

3875

5813

7750

9688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.463

Hom.:

57034

Bravo

AF:

0.449

Asia WGS

AF:

0.295

AC:

1027

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 08, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glanzmann thrombasthenia

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Apr 06, 2023

ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen

Significance:Benign

Review Status:reviewed by expert panel

Collection Method:curation

After a comprehensive literature search of the intronic variant NM_000212.3(ITGB3):c.2301+9C>T, no individuals with Glanzmann Thrombasthenia were reported with the variant. The variant has a high minor allele frequency of 0.4805 (11916/24800 alleles) in the African/African American population, which is higher than the ClinGen PD VCEP threshold (>0.0024), and therefore meets BA1. In silico predictor spliceAI revealed that the intronic mutation is not expected to impact splicing and a PhyloP score of -.336 shows that the nucleotide position is not highly conserved (BP4,BP7). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1, BP4 and BP7 (PD VCEP specifications version 2.1). -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.37

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over