rs70940817

Variant names:

• chr17-47300524-G-A
• rs70940817
• NM_000212.3:c.1960G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: This missense, c.1960G>A (p.Glu654Lys) variant occurs at an overall allele frequency in gnomAD of 0.0006917 with a MAF of 0.0005056 (138/19954 alleles, including 1 homozygote) in the East Asian population. Computational evidence does not support a deleterious effect on the gene/gene product. This variant meets criteria to be classified as Benign by the ClinGen Platelet Disorders VCEP. GT-specific criteria met: BA1. LINK:https://erepo.genome.network/evrepo/ui/classification/CA8623406/MONDO:0010119/011

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (1 hom.)
• Consequence: ITGB3 NM_000212.3 missense
• Clinical Significance: Benign reviewed by expert panel U:1 B:4
• Conservation: PhyloP100: 1.65
• 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]

ENSG00000259753 (HGNC:):

EFCAB13-DT (HGNC:55338): (EFCAB13 divergent transcript)

ACMG classification

Specifications for ITGB3 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: For more information check the summary or visit ClinGen Evidence Repository.

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.1960G>A	p.Glu654Lys	missense	Exon 12 of 15	NP_000203.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3	ENST00000559488.7	TSL:1 MANE Select	c.1960G>A	p.Glu654Lys	missense	Exon 12 of 15	ENSP00000452786.2	P05106-1
	ENSG00000259753	ENST00000560629.1	TSL:2	n.1924G>A		non_coding_transcript_exon	Exon 12 of 18	ENSP00000456711.2	H3BM21
	ITGB3	ENST00000696963.1		c.1960G>A	p.Glu654Lys	missense	Exon 12 of 14	ENSP00000513002.1	P05106-2

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000521 AC: 131 AN: 251436 AF XY: 0.000464

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00690

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000176 AC: 258 AN: 1461858 Hom.: 1 Cov.: 31 AF XY: 0.000164 AC XY: 119 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00564 AC: 224 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111992

Other (OTH) AF: 0.000298 AC: 18 AN: 60394

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152238 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74428

African (AFR) AF: 0.0000241 AC: 1 AN: 41544

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00521 AC: 27 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000357 Hom.: 0

Bravo AF: 0.000344

ExAC AF: 0.000535 AC: 65

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	2	Glanzmann thrombasthenia (2)
-	1	-	Glanzmann thrombasthenia;C5442010:Platelet-type bleeding disorder 16 (1)
-	-	1	ITGB3-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.7
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.76	N
Sift	Benign	0.30	T
Sift4G	Benign	0.40	T
Polyphen		0.0030	B
Vest4		0.77
MVP		0.92
MPC		0.46
ClinPred		0.024	T
GERP RS		4.1
Varity_R		0.11
gMVP		0.55
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs70940817; hg19: chr17-45377890; COSMIC: COSV71383566; COSMIC: COSV71383566;