NM_000212.3:c.80-667A>G

Variant names:

• chr17-47273752-A-G
• rs7209700
• NM_000212.3:c.80-667A>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.80-667A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,130 control chromosomes in the GnomAD database, including 9,322 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 (9322 hom., cov: 33)
• Consequence: ITGB3 NM_000212.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• Publications: 23 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3	NM_000212.3	MANE Select	c.80-667A>G		intron	N/A	NP_000203.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3	ENST00000559488.7	TSL:1 MANE Select	c.80-667A>G		intron	N/A	ENSP00000452786.2
	ITGB3	ENST00000571680.1	TSL:1	c.80-667A>G		intron	N/A	ENSP00000461626.1
	ENSG00000259753	ENST00000560629.1	TSL:2	n.44-667A>G		intron	N/A	ENSP00000456711.2

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52254 AN: 152012 Hom.: 9313 Cov.: 33

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.344 AC: 52296 AN: 152130 Hom.: 9322 Cov.: 33 AF XY: 0.342 AC XY: 25404 AN XY: 74366

African (AFR) AF: 0.405 AC: 16820 AN: 41492

American (AMR) AF: 0.304 AC: 4657 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1083 AN: 3470

East Asian (EAS) AF: 0.387 AC: 2001 AN: 5176

South Asian (SAS) AF: 0.352 AC: 1701 AN: 4826

European-Finnish (FIN) AF: 0.290 AC: 3060 AN: 10568

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21915 AN: 67990

Other (OTH) AF: 0.343 AC: 723 AN: 2108

Alfa AF: 0.328 Hom.: 26510

Bravo AF: 0.345

Asia WGS AF: 0.377 AC: 1309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.52
PhyloP100		0.18
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: rs7209700; hg19: chr17-45351118;