rs3809863

Variant names:

• chr17-47307646-C-T
• rs3809863
• NM_000212.3:c.2301+9C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP7 BA1 BP4

This summary comes from the ClinGen Evidence Repository: After a comprehensive literature search of the intronic variant NM_000212.3(ITGB3):c.2301+9C>T, no individuals with Glanzmann Thrombasthenia were reported with the variant. The variant has a high minor allele frequency of 0.4805 (11916/24800 alleles) in the African/African American population, which is higher than the ClinGen PD VCEP threshold (>0.0024), and therefore meets BA1. In silico predictor spliceAI revealed that the intronic mutation is not expected to impact splicing and a PhyloP score of -.336 shows that the nucleotide position is not highly conserved (BP4,BP7). 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 and BP7 (PD VCEP specifications version 2.1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA8623491/MONDO:0100326/011

• Frequency:
  • Genomes: 𝑓 0.46 (16187 hom., cov: 32)
  • Exomes 𝑓: 0.46 (158722 hom.)
• Consequence: ITGB3 NM_000212.3 intron
• Clinical Significance: Benign reviewed by expert panel B:6
• Conservation: PhyloP100: 0.370
• Publications: 38 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 -10 ACMG points.

• BP4: For more information check the summary or visit ClinGen Evidence Repository.
• BP7: 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.2301+9C>T		intron	N/A	NP_000203.2
	EFCAB13-DT	NR_110880.1		n.363-3864G>A		intron	N/A
	EFCAB13-DT	NR_110881.1		n.227-3864G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3	ENST00000559488.7	TSL:1 MANE Select	c.2301+9C>T		intron	N/A	ENSP00000452786.2	P05106-1
	ENSG00000259753	ENST00000560629.1	TSL:2	n.2265+9C>T		intron	N/A	ENSP00000456711.2	H3BM21
	ITGB3	ENST00000696963.1		c.2310C>T	p.Asp770Asp	synonymous	Exon 14 of 14	ENSP00000513002.1	P05106-2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69311 AN: 151934 Hom.: 16185 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.439

GnomAD2 exomes AF: 0.429 AC: 107220 AN: 249968 AF XY: 0.431

Gnomad AFR exome AF: 0.482

Gnomad AMR exome AF: 0.354

Gnomad ASJ exome AF: 0.419

Gnomad EAS exome AF: 0.249

Gnomad FIN exome AF: 0.494

Gnomad NFE exome AF: 0.472

Gnomad OTH exome AF: 0.432

GnomAD4 exome AF: 0.463 AC: 676003 AN: 1460176 Hom.: 158722 Cov.: 36 AF XY: 0.461 AC XY: 335190 AN XY: 726390

African (AFR) AF: 0.475 AC: 15897 AN: 33440

American (AMR) AF: 0.356 AC: 15872 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 10915 AN: 26120

East Asian (EAS) AF: 0.269 AC: 10683 AN: 39674

South Asian (SAS) AF: 0.389 AC: 33552 AN: 86166

European-Finnish (FIN) AF: 0.493 AC: 26318 AN: 53374

Middle Eastern (MID) AF: 0.388 AC: 2239 AN: 5766

European-Non Finnish (NFE) AF: 0.480 AC: 533193 AN: 1110700

Other (OTH) AF: 0.453 AC: 27334 AN: 60354

GnomAD4 genome AF: 0.456 AC: 69347 AN: 152052 Hom.: 16187 Cov.: 32 AF XY: 0.453 AC XY: 33674 AN XY: 74310

African (AFR) AF: 0.480 AC: 19888 AN: 41456

American (AMR) AF: 0.374 AC: 5714 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1501 AN: 3470

East Asian (EAS) AF: 0.252 AC: 1305 AN: 5180

South Asian (SAS) AF: 0.381 AC: 1835 AN: 4810

European-Finnish (FIN) AF: 0.499 AC: 5277 AN: 10572

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32356 AN: 67974

Other (OTH) AF: 0.438 AC: 924 AN: 2108

Alfa AF: 0.463 Hom.: 57034

Bravo AF: 0.449

Asia WGS AF: 0.295 AC: 1027 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Glanzmann thrombasthenia (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		0.37
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: rs3809863; hg19: chr17-45385012; COSMIC: COSV107525062; COSMIC: COSV107525062;