rs15908

Variant names:

• chr17-47290971-A-C
• rs15908
• NM_000212.3:c.1143A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-47290971-A-C
• chr17-47290971-A-T
• chr17-47290971-A-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The ITGB3 synonymous variant NM_000212.2:c.1143A>C is very common in control population databases, with an overall allele frequency of 0.38777 in gnomAD v2.1.1. Note that initial reports of variation at this nucleotide position referred to the current reference allele as the variant at this position (c.1143C>A; PMID:8878424, PMID:20020534, and PMID:25728920), however this reported "variant" is now considered the reference allele. In summary, this variant meets criteria to be classified as benign for GT. GT-specific criteria applied: BA1. LINK:https://erepo.genome.network/evrepo/ui/classification/CA8623175/MONDO:0010119/011

• Frequency:
  • Genomes: 𝑓 0.39 (12141 hom., cov: 31)
  • Exomes 𝑓: 0.37 (102526 hom.)
• Consequence: ITGB3 NM_000212.3 synonymous
• Clinical Significance: Benign reviewed by expert panel B:8
• Conservation: PhyloP100: -0.320
• Publications: 33 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 -8 ACMG points.

• BA1: For more information check the summary or visit ClinGen Evidence Repository.

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.1143A>C	p.Val381Val	synonymous	Exon 9 of 15	NP_000203.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB3	ENST00000559488.7	TSL:1 MANE Select	c.1143A>C	p.Val381Val	synonymous	Exon 9 of 15	ENSP00000452786.2	P05106-1
	ITGB3	ENST00000571680.1	TSL:1	c.1143A>C	p.Val381Val	synonymous	Exon 9 of 9	ENSP00000461626.1	I3L4X8
	ENSG00000259753	ENST00000560629.1	TSL:2	n.1107A>C		non_coding_transcript_exon	Exon 9 of 18	ENSP00000456711.2	H3BM21

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59904 AN: 151892 Hom.: 12119 Cov.: 31

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.420

GnomAD2 exomes AF: 0.387 AC: 97372 AN: 251452 AF XY: 0.392

Gnomad AFR exome AF: 0.432

Gnomad AMR exome AF: 0.288

Gnomad ASJ exome AF: 0.432

Gnomad EAS exome AF: 0.584

Gnomad FIN exome AF: 0.331

Gnomad NFE exome AF: 0.369

Gnomad OTH exome AF: 0.394

GnomAD4 exome AF: 0.370 AC: 541056 AN: 1461434 Hom.: 102526 Cov.: 38 AF XY: 0.373 AC XY: 271008 AN XY: 727032

African (AFR) AF: 0.440 AC: 14722 AN: 33474

American (AMR) AF: 0.297 AC: 13294 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 11168 AN: 26130

East Asian (EAS) AF: 0.559 AC: 22177 AN: 39696

South Asian (SAS) AF: 0.454 AC: 39136 AN: 86244

European-Finnish (FIN) AF: 0.333 AC: 17785 AN: 53386

Middle Eastern (MID) AF: 0.473 AC: 2727 AN: 5766

European-Non Finnish (NFE) AF: 0.357 AC: 396346 AN: 1111632

Other (OTH) AF: 0.393 AC: 23701 AN: 60382

GnomAD4 genome AF: 0.395 AC: 59972 AN: 152010 Hom.: 12141 Cov.: 31 AF XY: 0.394 AC XY: 29263 AN XY: 74318

African (AFR) AF: 0.431 AC: 17873 AN: 41424

American (AMR) AF: 0.368 AC: 5625 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1490 AN: 3470

East Asian (EAS) AF: 0.568 AC: 2939 AN: 5174

South Asian (SAS) AF: 0.462 AC: 2225 AN: 4820

European-Finnish (FIN) AF: 0.318 AC: 3365 AN: 10580

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25061 AN: 67952

Other (OTH) AF: 0.415 AC: 876 AN: 2110

Alfa AF: 0.371 Hom.: 5710

Bravo AF: 0.397

EpiCase AF: 0.375

EpiControl AF: 0.387

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Glanzmann thrombasthenia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.57
PhyloP100		-0.32
Mutation Taster		=97/3	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: rs15908; hg19: chr17-45368337; COSMIC: COSV107525056; COSMIC: COSV107525056;