rs2317676

Variant names:

• chr17-47310917-A-G
• rs2317676
• NM_000212.3:c.*713A>G

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.*713A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.095 in 156,824 control chromosomes in the GnomAD database, including 797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.096 (789 hom., cov: 32)
  • Exomes 𝑓: 0.059 (8 hom.)
• Consequence: ITGB3 NM_000212.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0500
• Publications: 42 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-47310917-A-G is Benign according to our data. Variant chr17-47310917-A-G is described in ClinVar as Benign. ClinVar VariationId is 323887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB3	NM_000212.3	c.*713A>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000559488.7	NP_000203.2
EFCAB13-DT	NR_110880.1	n.363-7135T>C		intron_variant	Intron 2 of 2
EFCAB13-DT	NR_110881.1	n.227-7135T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7	c.*713A>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_000212.3	ENSP00000452786.2
ENSG00000259753	ENST00000560629.1	n.2265+3280A>G		intron_variant	Intron 14 of 17	2		ENSP00000456711.2

Frequencies

GnomAD3 genomes AF: 0.0961 AC: 14620 AN: 152136 Hom.: 786 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0870

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0726

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0586 AC: 268 AN: 4570 Hom.: 8 Cov.: 0 AF XY: 0.0622 AC XY: 148 AN XY: 2378

African (AFR) AF: 0.0769 AC: 2 AN: 26

American (AMR) AF: 0.0530 AC: 63 AN: 1188

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 2 AN: 20

East Asian (EAS) AF: 0.0714 AC: 9 AN: 126

South Asian (SAS) AF: 0.0806 AC: 25 AN: 310

European-Finnish (FIN) AF: 0.0321 AC: 14 AN: 436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0614 AC: 142 AN: 2314

Other (OTH) AF: 0.0743 AC: 11 AN: 148

GnomAD4 genome AF: 0.0961 AC: 14638 AN: 152254 Hom.: 789 Cov.: 32 AF XY: 0.0946 AC XY: 7047 AN XY: 74464

African (AFR) AF: 0.133 AC: 5542 AN: 41544

American (AMR) AF: 0.0869 AC: 1330 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3464

East Asian (EAS) AF: 0.189 AC: 978 AN: 5180

South Asian (SAS) AF: 0.118 AC: 571 AN: 4822

European-Finnish (FIN) AF: 0.0354 AC: 376 AN: 10612

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0727 AC: 4943 AN: 68020

Other (OTH) AF: 0.101 AC: 213 AN: 2106

Alfa AF: 0.0835 Hom.: 2439

Bravo AF: 0.103

Asia WGS AF: 0.141 AC: 491 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Glanzmann thrombasthenia Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.0
DANN	Benign	0.75
PhyloP100		0.050
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2317676; hg19: chr17-45388283;