rs4642

Variant names:

• chr17-47292411-A-G
• rs4642
• NM_000212.3:c.1533A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-47292411-A-G
• chr17-47292411-A-T
• chr17-47292411-A-C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BA1 BP4

This summary comes from the ClinGen Evidence Repository: After a comprehensive literature search of the synonymous variant NM_000212.3(ITGB3):c.1533A>G (p.Glu511=), no individuals with Glanzmann thrombasthenia were reported with the variant. Moreover, the variant has a minor allele frequency of 0.3455 (6891/19944) in gnomAD, found in the East Asian population, which is considerably higher than the expected frequency of the disease (BA1). In silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing (BP4). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1, BP4 (PD VCEP specifications version 2.1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA8623279/MONDO:0100326/011

• Frequency:
  • Genomes: 𝑓 0.29 (6393 hom., cov: 33)
  • Exomes 𝑓: 0.29 (61592 hom.)
• Consequence: ITGB3 NM_000212.3 synonymous
• Clinical Significance: Benign reviewed by expert panel B:8
• Conservation: PhyloP100: 2.13
• Publications: 33 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

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: For more information check the summary or visit ClinGen Evidence Repository.
• 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.1533A>G	p.Glu511Glu	synonymous	Exon 10 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.1533A>G	p.Glu511Glu	synonymous	Exon 10 of 15	ENSP00000452786.2	P05106-1
	ENSG00000259753	ENST00000560629.1	TSL:2	n.1497A>G		non_coding_transcript_exon	Exon 10 of 18	ENSP00000456711.2	H3BM21
	ITGB3	ENST00000696963.1		c.1533A>G	p.Glu511Glu	synonymous	Exon 10 of 14	ENSP00000513002.1	P05106-2

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43526 AN: 152034 Hom.: 6383 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.306

GnomAD2 exomes AF: 0.286 AC: 71739 AN: 250598 AF XY: 0.289

Gnomad AFR exome AF: 0.266

Gnomad AMR exome AF: 0.230

Gnomad ASJ exome AF: 0.290

Gnomad EAS exome AF: 0.345

Gnomad FIN exome AF: 0.291

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.292

GnomAD4 exome AF: 0.289 AC: 422482 AN: 1460006 Hom.: 61592 Cov.: 39 AF XY: 0.289 AC XY: 210104 AN XY: 725966

African (AFR) AF: 0.274 AC: 9154 AN: 33442

American (AMR) AF: 0.235 AC: 10515 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 7526 AN: 26102

East Asian (EAS) AF: 0.341 AC: 13541 AN: 39658

South Asian (SAS) AF: 0.294 AC: 25348 AN: 86232

European-Finnish (FIN) AF: 0.291 AC: 15512 AN: 53316

Middle Eastern (MID) AF: 0.300 AC: 1727 AN: 5760

European-Non Finnish (NFE) AF: 0.290 AC: 321511 AN: 1110502

Other (OTH) AF: 0.293 AC: 17648 AN: 60302

GnomAD4 genome AF: 0.286 AC: 43560 AN: 152154 Hom.: 6393 Cov.: 33 AF XY: 0.285 AC XY: 21232 AN XY: 74374

African (AFR) AF: 0.265 AC: 11006 AN: 41500

American (AMR) AF: 0.280 AC: 4279 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 979 AN: 3472

East Asian (EAS) AF: 0.333 AC: 1721 AN: 5174

South Asian (SAS) AF: 0.294 AC: 1417 AN: 4822

European-Finnish (FIN) AF: 0.283 AC: 2994 AN: 10592

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20196 AN: 67992

Other (OTH) AF: 0.303 AC: 640 AN: 2114

Alfa AF: 0.292 Hom.: 11259

Bravo AF: 0.282

Asia WGS AF: 0.337 AC: 1171 AN: 3478

EpiCase AF: 0.297

EpiControl AF: 0.304

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Glanzmann thrombasthenia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.3
DANN	Benign	0.54
PhyloP100		2.1
Mutation Taster		=96/4	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: rs4642; hg19: chr17-45369777; COSMIC: COSV71383876; COSMIC: COSV71383876;