chr17-47253882-C-G

Variant names:

• chr17-47253882-C-G
• rs1027548991
• NM_000212.3:c.21C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000212.3(ITGB3):​c.21C>G​(p.Pro7Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000178 in 1,123,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: ITGB3 NM_000212.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0670
• Publications: 0 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]

ITGB3 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 16

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Glanzmann thrombasthenia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Glanzmann thrombasthenia 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• bleeding disorder, platelet-type, 24

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant macrothrombocytopenia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Glanzmann's thrombasthenia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000259753 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 17-47253882-C-G is Benign according to our data. Variant chr17-47253882-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2907326.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.067 with no splicing effect.

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.21C>G	p.Pro7Pro	synonymous	Exon 1 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.21C>G	p.Pro7Pro	synonymous	Exon 1 of 15	ENSP00000452786.2	P05106-1
	ITGB3	ENST00000571680.1	TSL:1	c.21C>G	p.Pro7Pro	synonymous	Exon 1 of 9	ENSP00000461626.1	I3L4X8
	ITGB3	ENST00000696963.1		c.21C>G	p.Pro7Pro	synonymous	Exon 1 of 14	ENSP00000513002.1	P05106-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000178 AC: 2 AN: 1123520 Hom.: 0 Cov.: 30 AF XY: 0.00000185 AC XY: 1 AN XY: 540508

African (AFR) AF: 0.00 AC: 0 AN: 23250

American (AMR) AF: 0.00 AC: 0 AN: 11288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16408

East Asian (EAS) AF: 0.00 AC: 0 AN: 26328

South Asian (SAS) AF: 0.00 AC: 0 AN: 31252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3180

European-Non Finnish (NFE) AF: 0.00000212 AC: 2 AN: 942282

Other (OTH) AF: 0.00 AC: 0 AN: 44874

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.2
DANN	Benign	0.75
PhyloP100		0.067
PromoterAI		0.084	Neutral

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: rs1027548991; hg19: chr17-45331248;