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 (★★). The gene ITGB3 is included in the ClinGen Criteria Specification Registry.

• 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: 43 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

Specifications for ITGB3 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

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.

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.*713A>G		3_prime_UTR	Exon 15 of 15	NP_000203.2
	EFCAB13-DT	NR_110880.1		n.363-7135T>C		intron	N/A
	EFCAB13-DT	NR_110881.1		n.227-7135T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3	ENST00000559488.7	TSL:1 MANE Select	c.*713A>G		3_prime_UTR	Exon 15 of 15	ENSP00000452786.2	P05106-1
	ENSG00000259753	ENST00000560629.1	TSL:2	n.2265+3280A>G		intron	N/A	ENSP00000456711.2	H3BM21
	EFCAB13-DT	ENST00000575039.1	TSL:5	n.227-7135T>C		intron	N/A

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

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;