rs2015729

Variant names:

• chr17-47277127-G-A
• rs2015729
• NM_000212.3:c.165+2623G>A

Variant summary

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

The NM_000212.3(ITGB3):​c.165+2623G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,886 control chromosomes in the GnomAD database, including 13,316 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 0.41 (13316 hom., cov: 31)
• Consequence: ITGB3 NM_000212.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB3	NM_000212.3	c.165+2623G>A		intron_variant	Intron 2 of 14	ENST00000559488.7	NP_000203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7	c.165+2623G>A		intron_variant	Intron 2 of 14	1	NM_000212.3	ENSP00000452786.2
ITGB3	ENST00000571680.1	c.165+2623G>A		intron_variant	Intron 2 of 8	1		ENSP00000461626.1
ENSG00000259753	ENST00000560629.1	n.129+2623G>A		intron_variant	Intron 2 of 17	2		ENSP00000456711.2
ITGB3	ENST00000696963.1	c.165+2623G>A		intron_variant	Intron 2 of 13			ENSP00000513002.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62786 AN: 151768 Hom.: 13291 Cov.: 31

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.414 AC: 62856 AN: 151886 Hom.: 13316 Cov.: 31 AF XY: 0.412 AC XY: 30592 AN XY: 74246

African (AFR) AF: 0.451 AC: 18677 AN: 41376

American (AMR) AF: 0.383 AC: 5845 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1595 AN: 3472

East Asian (EAS) AF: 0.573 AC: 2962 AN: 5166

South Asian (SAS) AF: 0.468 AC: 2253 AN: 4816

European-Finnish (FIN) AF: 0.326 AC: 3435 AN: 10552

Middle Eastern (MID) AF: 0.503 AC: 146 AN: 290

European-Non Finnish (NFE) AF: 0.392 AC: 26651 AN: 67926

Other (OTH) AF: 0.437 AC: 919 AN: 2102

Alfa AF: 0.395 Hom.: 5111

Bravo AF: 0.418

Asia WGS AF: 0.512 AC: 1779 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	2.3
DANN	Benign	0.85
PhyloP100		0.072
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: rs2015729; hg19: chr17-45354493;