rs11870252

Variant names:

• chr17-47300459-T-C
• rs11870252
• NM_000212.3:c.1914-19T>C

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.1914-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 1,594,948 control chromosomes in the GnomAD database, including 5,629 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (606 hom., cov: 32)
  • Exomes 𝑓: 0.077 (5023 hom.)
• Consequence: ITGB3 NM_000212.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.383
• Publications: 11 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=-0.87).
• BP6: Variant 17-47300459-T-C is Benign according to our data. Variant chr17-47300459-T-C is described in ClinVar as Benign. ClinVar VariationId is 255538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3	NM_000212.3	MANE Select	c.1914-19T>C		intron	N/A	NP_000203.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3	ENST00000559488.7	TSL:1 MANE Select	c.1914-19T>C		intron	N/A	ENSP00000452786.2
	ENSG00000259753	ENST00000560629.1	TSL:2	n.1878-19T>C		intron	N/A	ENSP00000456711.2
	ITGB3	ENST00000696963.1		c.1914-19T>C		intron	N/A	ENSP00000513002.1

Frequencies

GnomAD3 genomes AF: 0.0858 AC: 13044 AN: 152098 Hom.: 605 Cov.: 32

Gnomad AFR AF: 0.0968

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0833

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0723

Gnomad OTH AF: 0.0985

GnomAD2 exomes AF: 0.0885 AC: 22219 AN: 251082 AF XY: 0.0909

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.0552

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.192

Gnomad FIN exome AF: 0.0392

Gnomad NFE exome AF: 0.0759

Gnomad OTH exome AF: 0.0982

GnomAD4 exome AF: 0.0766 AC: 110569 AN: 1442732 Hom.: 5023 Cov.: 28 AF XY: 0.0782 AC XY: 56235 AN XY: 718980

African (AFR) AF: 0.0931 AC: 3081 AN: 33100

American (AMR) AF: 0.0595 AC: 2660 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3645 AN: 26022

East Asian (EAS) AF: 0.186 AC: 7382 AN: 39596

South Asian (SAS) AF: 0.120 AC: 10309 AN: 85854

European-Finnish (FIN) AF: 0.0416 AC: 2221 AN: 53326

Middle Eastern (MID) AF: 0.162 AC: 930 AN: 5742

European-Non Finnish (NFE) AF: 0.0685 AC: 75033 AN: 1094648

Other (OTH) AF: 0.0888 AC: 5308 AN: 59744

GnomAD4 genome AF: 0.0858 AC: 13055 AN: 152216 Hom.: 606 Cov.: 32 AF XY: 0.0852 AC XY: 6343 AN XY: 74422

African (AFR) AF: 0.0967 AC: 4016 AN: 41540

American (AMR) AF: 0.0832 AC: 1272 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3472

East Asian (EAS) AF: 0.192 AC: 994 AN: 5172

South Asian (SAS) AF: 0.118 AC: 571 AN: 4820

European-Finnish (FIN) AF: 0.0350 AC: 372 AN: 10616

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.0724 AC: 4924 AN: 67994

Other (OTH) AF: 0.0970 AC: 205 AN: 2114

Alfa AF: 0.0815 Hom.: 186

Bravo AF: 0.0910

Asia WGS AF: 0.138 AC: 481 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.039
DANN	Benign	0.27
PhyloP100		-0.38
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: rs11870252; hg19: chr17-45377825; COSMIC: COSV71383619; COSMIC: COSV71383619;