rs117052258

Positions:

• chr17-47253855-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB3	NM_000212.3	c.-7G>C		5_prime_UTR_variant	1/15	ENST00000559488.7	NP_000203.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7	c.-7G>C		5_prime_UTR_variant	1/15	1	NM_000212.3	ENSP00000452786	P1
ITGB3	ENST00000571680.1	c.-7G>C		5_prime_UTR_variant	1/9	1		ENSP00000461626
ITGB3	ENST00000696963.1	c.-7G>C		5_prime_UTR_variant	1/14			ENSP00000513002

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

GnomAD3 exomes AF: 0.0345 AC: 78 AN: 2262 Hom.: 2 AF XY: 0.0322 AC XY: 52 AN XY: 1614

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 SAS exome AF: 0.110

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

Gnomad4 AFR exome AF: 0.00483

Gnomad4 AMR exome AF: 0.0182

Gnomad4 ASJ exome AF: 0.0302

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.0891

Gnomad4 FIN exome AF: 0.0329

Gnomad4 NFE exome AF: 0.0229

Gnomad4 OTH exome AF: 0.0417

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

Gnomad4 AFR AF: 0.00637

Gnomad4 AMR AF: 0.0242

Gnomad4 ASJ AF: 0.0358

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0273

Gnomad4 NFE AF: 0.0244

Gnomad4 OTH AF: 0.0318

Alfa AF: 0.0237 Hom.: 9

Bravo AF: 0.0282

Asia WGS AF: 0.138 AC: 476 AN: 3444

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Glanzmann thrombasthenia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs117052258; hg19: chr17-45331221;