rs117052258

Variant names:

• chr17-47253855-G-C
• rs117052258
• NM_000212.3:c.-7G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-47253855-G-C
• chr17-47253855-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000212.3(ITGB3):​c.-7G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 1,219,630 control chromosomes in the GnomAD database, including 1,156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (211 hom., cov: 32)
  • Exomes 𝑓: 0.029 (945 hom.)
• Consequence: ITGB3 NM_000212.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.331
• Publications: 4 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):

• platelet-type bleeding disorder 16

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• 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)
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 17-47253855-G-C is Benign according to our data. Variant chr17-47253855-G-C is described in ClinVar as Benign. ClinVar VariationId is 255534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

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.-7G>C		5_prime_UTR	Exon 1 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.-7G>C		5_prime_UTR	Exon 1 of 15	ENSP00000452786.2	P05106-1
	ITGB3	ENST00000571680.1	TSL:1	c.-7G>C		5_prime_UTR	Exon 1 of 9	ENSP00000461626.1	I3L4X8
	ITGB3	ENST00000696963.1		c.-7G>C		5_prime_UTR	Exon 1 of 14	ENSP00000513002.1	P05106-2

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4414 AN: 151572 Hom.: 213 Cov.: 32

Gnomad AFR AF: 0.00638

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.0358

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0243

Gnomad OTH AF: 0.0326

GnomAD2 exomes AF: 0.0345 AC: 78 AN: 2262 AF XY: 0.0322

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.500

Gnomad FIN exome AF: 0.0278

Gnomad NFE exome AF: 0.0200

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0290 AC: 30954 AN: 1067952 Hom.: 945 Cov.: 29 AF XY: 0.0292 AC XY: 14799 AN XY: 506386

African (AFR) AF: 0.00483 AC: 107 AN: 22166

American (AMR) AF: 0.0182 AC: 143 AN: 7870

Ashkenazi Jewish (ASJ) AF: 0.0302 AC: 406 AN: 13432

East Asian (EAS) AF: 0.200 AC: 4998 AN: 25030

South Asian (SAS) AF: 0.0891 AC: 1819 AN: 20412

European-Finnish (FIN) AF: 0.0329 AC: 708 AN: 21526

Middle Eastern (MID) AF: 0.0322 AC: 93 AN: 2886

European-Non Finnish (NFE) AF: 0.0229 AC: 20915 AN: 912266

Other (OTH) AF: 0.0417 AC: 1765 AN: 42364

GnomAD4 genome AF: 0.0291 AC: 4411 AN: 151678 Hom.: 211 Cov.: 32 AF XY: 0.0318 AC XY: 2356 AN XY: 74152

African (AFR) AF: 0.00637 AC: 264 AN: 41468

American (AMR) AF: 0.0242 AC: 368 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0358 AC: 124 AN: 3464

East Asian (EAS) AF: 0.226 AC: 1155 AN: 5102

South Asian (SAS) AF: 0.101 AC: 487 AN: 4826

European-Finnish (FIN) AF: 0.0273 AC: 285 AN: 10436

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.0244 AC: 1653 AN: 67838

Other (OTH) AF: 0.0318 AC: 67 AN: 2106

Alfa AF: 0.0237 Hom.: 9

Bravo AF: 0.0282

Asia WGS AF: 0.138 AC: 476 AN: 3444

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		0.33
PromoterAI		0.0054	Neutral
Mutation Taster		=297/3	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: rs117052258; hg19: chr17-45331221;