rs2292863

Positions:

• chr17-47291764-C-G
• chr17-47291764-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000212.3(ITGB3):​c.1261-375C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,046 control chromosomes in the GnomAD database, including 6,391 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6391 hom., cov: 32)
• Consequence: ITGB3 NM_000212.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB3	NM_000212.3	c.1261-375C>G		intron_variant		ENST00000559488.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB3	ENST00000559488.7	c.1261-375C>G		intron_variant		1	NM_000212.3	P1
ITGB3	ENST00000573377.1	c.*267+337C>G		intron_variant, NMD_transcript_variant		1
ITGB3	ENST00000696963.1	c.1261-375C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43509 AN: 151928 Hom.: 6382 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.307

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.286 AC: 43541 AN: 152046 Hom.: 6391 Cov.: 32 AF XY: 0.286 AC XY: 21245 AN XY: 74352

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.304

Alfa AF: 0.288 Hom.: 818

Bravo AF: 0.282

Asia WGS AF: 0.337 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.3
DANN	Benign	0.78

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: rs2292863; hg19: chr17-45369130;