chr17-47264763-G-T

Variant names:

• chr17-47264763-G-T
• rs10514919
• NM_000212.3:c.80-9656G>T

Variant summary

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

The NM_000212.3(ITGB3):​c.80-9656G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,990 control chromosomes in the GnomAD database, including 5,575 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 (5575 hom., cov: 32)
• Consequence: ITGB3 NM_000212.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100
• Publications: 19 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 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.80-9656G>T		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.80-9656G>T		intron	N/A	ENSP00000452786.2
	ITGB3	ENST00000571680.1	TSL:1	c.80-9656G>T		intron	N/A	ENSP00000461626.1
	ENSG00000259753	ENST00000560629.1	TSL:2	n.44-9656G>T		intron	N/A	ENSP00000456711.2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40192 AN: 151872 Hom.: 5573 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.265 AC: 40217 AN: 151990 Hom.: 5575 Cov.: 32 AF XY: 0.262 AC XY: 19478 AN XY: 74282

African (AFR) AF: 0.323 AC: 13381 AN: 41438

American (AMR) AF: 0.187 AC: 2853 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3466

East Asian (EAS) AF: 0.236 AC: 1217 AN: 5164

South Asian (SAS) AF: 0.251 AC: 1212 AN: 4822

European-Finnish (FIN) AF: 0.270 AC: 2849 AN: 10560

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.253 AC: 17177 AN: 67948

Other (OTH) AF: 0.260 AC: 550 AN: 2112

Alfa AF: 0.249 Hom.: 14410

Bravo AF: 0.259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		-0.10
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: rs10514919; hg19: chr17-45342129;