rs2317676

Positions:

• chr17-47310917-A-G

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.*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

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]

EFCAB13-DT (HGNC:55338): (EFCAB13 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
ITGB3	NM_000212.3	c.*713A>G		3_prime_UTR_variant	15/15	ENST00000559488.7	NP_000203.2
EFCAB13-DT	NR_110880.1	n.363-7135T>C		intron_variant, non_coding_transcript_variant
EFCAB13-DT	NR_110881.1	n.227-7135T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB3	ENST00000559488.7	c.*713A>G		3_prime_UTR_variant	15/15	1	NM_000212.3	ENSP00000452786	P1
EFCAB13-DT	ENST00000575039.1	n.227-7135T>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.0769

Gnomad4 AMR exome AF: 0.0530

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.0714

Gnomad4 SAS exome AF: 0.0806

Gnomad4 FIN exome AF: 0.0321

Gnomad4 NFE exome AF: 0.0614

Gnomad4 OTH exome AF: 0.0743

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

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0869

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0354

Gnomad4 NFE AF: 0.0727

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0817 Hom.: 983

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 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	-0.81
CADD	Benign	9.0
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2317676; hg19: chr17-45388283;