rs6069

Variant names:

• chr3-129061871-G-A
• rs6069
• NM_000174.5:c.132G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-129061871-G-A
• chr3-129061871-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.51
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• Bernard-Soulier syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.132G>A	p.Thr44Thr	synonymous_variant	Exon 3 of 3	ENST00000307395.5	NP_000165.1
GP9	XM_047447997.1	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	c.132G>A	p.Thr44Thr	synonymous_variant	Exon 3 of 3	1	NM_000174.5	ENSP00000303942.4

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 5438 AN: 152158 Hom.: 230 Cov.: 33

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

GnomAD2 exomes AF: 0.0238 AC: 5799 AN: 243794 AF XY: 0.0241

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 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.: 32 AF XY: 0.0115 AC XY: 8331 AN XY: 726590

African (AFR) AF: 0.105 AC: 3501 AN: 33460

American (AMR) AF: 0.00551 AC: 246 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.00199 AC: 52 AN: 26080

East Asian (EAS) AF: 0.0625 AC: 2478 AN: 39630

South Asian (SAS) AF: 0.0634 AC: 5465 AN: 86164

European-Finnish (FIN) AF: 0.0158 AC: 832 AN: 52790

Middle Eastern (MID) AF: 0.0102 AC: 59 AN: 5764

European-Non Finnish (NFE) AF: 0.00112 AC: 1240 AN: 1111642

Other (OTH) AF: 0.0136 AC: 821 AN: 60322

GnomAD4 genome AF: 0.0358 AC: 5453 AN: 152276 Hom.: 231 Cov.: 33 AF XY: 0.0367 AC XY: 2731 AN XY: 74460

African (AFR) AF: 0.101 AC: 4210 AN: 41538

American (AMR) AF: 0.0120 AC: 184 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3468

East Asian (EAS) AF: 0.0745 AC: 386 AN: 5184

South Asian (SAS) AF: 0.0702 AC: 339 AN: 4830

European-Finnish (FIN) AF: 0.0167 AC: 177 AN: 10630

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00154 AC: 105 AN: 68006

Other (OTH) AF: 0.0209 AC: 44 AN: 2110

Alfa AF: 0.00432 Hom.: 13

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

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6069; hg19: chr3-128780714; COSMIC: COSV56624952;