rs6069

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000174.5(GP9):c.132G>A(p.Thr44Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,612,758 control chromosomes in the GnomAD database, including 761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 231 hom., cov: 33)

Exomes 𝑓: 0.010 ( 530 hom. )

Consequence

GP9
NM_000174.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.51

Variant links:

Genes affected

GP9 (HGNC:4444): (glycoprotein IX platelet) This gene encodes a small membrane glycoprotein found on the surface of human platelets. It forms a 1-to-1 noncovalent complex with glycoprotein Ib, a platelet surface membrane glycoprotein complex that functions as a receptor for von Willebrand factor. The complete receptor complex includes noncovalent association of the alpha and beta subunits with the protein encoded by this gene and platelet glycoprotein V. Defects in this gene are a cause of Bernard-Soulier syndrome, also known as giant platelet disease. These patients have unusually large platelets and have a clinical bleeding tendency. [provided by RefSeq, Oct 2008]

GP9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 3-129061871-G-A is Benign according to our data. Variant chr3-129061871-G-A is described in ClinVar as [Benign]. Clinvar id is 255471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP9	NM_000174.5 link	c.132G>A	p.Thr44Thr	synonymous_variant	Exon 3 of 3	ENST00000307395.5	NP_000165.1	P14770
GP9	XM_047447997.1 link	c.132G>A	p.Thr44Thr	synonymous_variant	Exon 2 of 2		XP_047303953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP9	ENST00000307395.5 link	c.132G>A	p.Thr44Thr	synonymous_variant	Exon 3 of 3	1	NM_000174.5	ENSP00000303942.4		P14770

Frequencies

GnomAD3 genomes

AF:

0.0357

AC:

5438

AN:

152158

Hom.:

230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0745

Gnomad SAS

AF:

0.0703

Gnomad FIN

AF:

0.0167

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00154

Gnomad OTH

AF:

0.0211

GnomAD3 exomes

AF:

0.0238

AC:

5799

AN:

243794

Hom.:

216

AF XY:

0.0241

AC XY:

3194

AN XY:

132678

show subpopulations

Gnomad AFR exome

AF:

0.0997

Gnomad AMR exome

AF:

0.00491

Gnomad ASJ exome

AF:

0.00192

Gnomad EAS exome

AF:

0.0810

Gnomad SAS exome

AF:

0.0664

Gnomad FIN exome

AF:

0.0166

Gnomad NFE exome

AF:

0.00156

Gnomad OTH exome

AF:

0.0105

GnomAD4 exome

AF:

0.0101

AC:

14694

AN:

1460482

Hom.:

530

Cov.:

AF XY:

0.0115

AC XY:

8331

AN XY:

726590

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.00551

Gnomad4 ASJ exome

AF:

0.00199

Gnomad4 EAS exome

AF:

0.0625

Gnomad4 SAS exome

AF:

0.0634

Gnomad4 FIN exome

AF:

0.0158

Gnomad4 NFE exome

AF:

0.00112

Gnomad4 OTH exome

AF:

0.0136

GnomAD4 genome

AF:

0.0358

AC:

5453

AN:

152276

Hom.:

231

Cov.:

AF XY:

0.0367

AC XY:

2731

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.0120

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.0745

Gnomad4 SAS

AF:

0.0702

Gnomad4 FIN

AF:

0.0167

Gnomad4 NFE

AF:

0.00154

Gnomad4 OTH

AF:

0.0209

Alfa

AF:

0.00432

Hom.:

Bravo

AF:

0.0372

Asia WGS

AF:

0.0630

AC:

219

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00125

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bernard Soulier syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over