17-47273553-G-C

Variant names:

• chr17-47273553-G-C
• rs3851806
• NM_000212.3:c.80-866G>C

Variant summary

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

The NM_000212.3(ITGB3):​c.80-866G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,130 control chromosomes in the GnomAD database, including 2,902 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 0.19 (2902 hom., cov: 32)
• Consequence: ITGB3 NM_000212.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB3	NM_000212.3	c.80-866G>C		intron_variant	Intron 1 of 14	ENST00000559488.7	NP_000203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7	c.80-866G>C		intron_variant	Intron 1 of 14	1	NM_000212.3	ENSP00000452786.2
ITGB3	ENST00000571680.1	c.80-866G>C		intron_variant	Intron 1 of 8	1		ENSP00000461626.1
ENSG00000259753	ENST00000560629.1	n.44-866G>C		intron_variant	Intron 1 of 17	2		ENSP00000456711.2
ITGB3	ENST00000696963.1	c.80-866G>C		intron_variant	Intron 1 of 13			ENSP00000513002.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28945 AN: 152012 Hom.: 2895 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.190 AC: 28977 AN: 152130 Hom.: 2902 Cov.: 32 AF XY: 0.191 AC XY: 14221 AN XY: 74390

African (AFR) AF: 0.222 AC: 9199 AN: 41490

American (AMR) AF: 0.196 AC: 2993 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3466

East Asian (EAS) AF: 0.324 AC: 1677 AN: 5176

South Asian (SAS) AF: 0.221 AC: 1066 AN: 4814

European-Finnish (FIN) AF: 0.156 AC: 1651 AN: 10590

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11251 AN: 67984

Other (OTH) AF: 0.187 AC: 395 AN: 2108

Alfa AF: 0.0733 Hom.: 78

Bravo AF: 0.193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.75
DANN	Benign	0.37
PhyloP100		-0.49
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: rs3851806; hg19: chr17-45350919;