rs2056131

Variant names:

• chr17-47256377-A-G
• rs2056131
• NM_000212.3:c.79+2437A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000212.3(ITGB3):​c.79+2437A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,900 control chromosomes in the GnomAD database, including 32,238 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 0.65 (32238 hom., cov: 30)
• Consequence: ITGB3 NM_000212.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.581
• Publications: 16 publications found

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

ENSG00000259753 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000212.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3	NM_000212.3	MANE Select	c.79+2437A>G		intron	N/A	NP_000203.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3	ENST00000559488.7	TSL:1 MANE Select	c.79+2437A>G		intron	N/A	ENSP00000452786.2
	ITGB3	ENST00000571680.1	TSL:1	c.79+2437A>G		intron	N/A	ENSP00000461626.1
	ENSG00000259753	ENST00000560629.1	TSL:2	n.43+2437A>G		intron	N/A	ENSP00000456711.2

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98350 AN: 151782 Hom.: 32213 Cov.: 30

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.648 AC: 98420 AN: 151900 Hom.: 32238 Cov.: 30 AF XY: 0.648 AC XY: 48097 AN XY: 74266

African (AFR) AF: 0.579 AC: 23964 AN: 41372

American (AMR) AF: 0.551 AC: 8404 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2478 AN: 3466

East Asian (EAS) AF: 0.653 AC: 3371 AN: 5164

South Asian (SAS) AF: 0.728 AC: 3495 AN: 4802

European-Finnish (FIN) AF: 0.706 AC: 7448 AN: 10550

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47056 AN: 67964

Other (OTH) AF: 0.653 AC: 1377 AN: 2110

Alfa AF: 0.681 Hom.: 37597

Bravo AF: 0.629

Asia WGS AF: 0.661 AC: 2301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.8
DANN	Benign	0.73
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2056131; hg19: chr17-45333743;