Genetic Variant NM_000212.3:c.165+1065C>T (chr17-47275569-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.165+1065C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,194 control chromosomes in the GnomAD database, including 1,381 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 0.13 ( 1381 hom., cov: 32)

Consequence

ITGB3
NM_000212.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.724

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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB3	NM_000212.3 link	c.165+1065C>T		intron_variant	Intron 2 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.165+1065C>T	intron_variant	Intron 2 of 14	1	NM_000212.3	ENSP00000452786.2	P05106-1
ITGB3	ENST00000571680.1 link	c.165+1065C>T	intron_variant	Intron 2 of 8	1		ENSP00000461626.1	I3L4X8
ENSG00000259753	ENST00000560629.1 link	n.129+1065C>T	intron_variant	Intron 2 of 17	2		ENSP00000456711.2	H3BM21
ITGB3	ENST00000696963.1 link	c.165+1065C>T	intron_variant	Intron 2 of 13			ENSP00000513002.1	P05106-2

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19468

AN:

152076

Hom.:

1381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.00616

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.143

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

GnomAD4 genome

AF:

0.128

AC:

19467

AN:

152194

Hom.:

1381

Cov.:

AF XY:

0.125

AC XY:

9322

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.105

AC:

4363

AN:

41520

American (AMR)

AF:

0.102

AC:

1563

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

494

AN:

3470

East Asian (EAS)

AF:

0.00656

AC:

AN:

5180

South Asian (SAS)

AF:

0.101

AC:

484

AN:

4814

European-Finnish (FIN)

AF:

0.134

AC:

1421

AN:

10602

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.156

AC:

10631

AN:

67988

Other (OTH)

AF:

0.142

AC:

299

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

870

1740

2609

3479

4349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.137

Hom.:

2430

Bravo

AF:

0.124

Asia WGS

AF:

0.0610

AC:

215

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.38

(source)

DANN

Benign

0.41

PhyloP100

-0.72

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