rs892089

Variant names:

• chr19-55027693-A-G
• rs892089
• NM_001083899.2:c.495T>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_001083899.2(GP6):​c.495T>C​(p.Phe165Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,611,254 control chromosomes in the GnomAD database, including 521,271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44637 hom., cov: 33)
  • Exomes 𝑓: 0.81 (476634 hom.)
• Consequence: GP6 NM_001083899.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0460
• Publications: 19 publications found

Genes affected

GP6 (HGNC:14388): (glycoprotein VI platelet) This gene encodes a platelet membrane glycoprotein of the immunoglobulin superfamily. The encoded protein is a receptor for collagen and plays a critical role in collagen-induced platelet aggregation and thrombus formation. The encoded protein forms a complex with the Fc receptor gamma-chain that initiates the platelet activation signaling cascade upon collagen binding. Mutations in this gene are a cause of platelet-type bleeding disorder-11 (BDPLT11). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ENSG00000267149 (HGNC:):

GP6-AS1 (HGNC:55305): (GP6 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-55027693-A-G is Benign according to our data. Variant chr19-55027693-A-G is described in ClinVar as Benign. ClinVar VariationId is 257419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.046 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP6	NM_001083899.2	c.495T>C	p.Phe165Phe	synonymous_variant	Exon 4 of 8	ENST00000310373.7	NP_001077368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7	c.495T>C	p.Phe165Phe	synonymous_variant	Exon 4 of 8	1	NM_001083899.2	ENSP00000308782.3
GP6	ENST00000417454.5	c.495T>C	p.Phe165Phe	synonymous_variant	Exon 4 of 8	1		ENSP00000394922.1

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115429 AN: 152002 Hom.: 44627 Cov.: 33

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.790

GnomAD2 exomes AF: 0.799 AC: 199303 AN: 249510 AF XY: 0.798

Gnomad AFR exome AF: 0.586

Gnomad AMR exome AF: 0.831

Gnomad ASJ exome AF: 0.786

Gnomad EAS exome AF: 0.835

Gnomad FIN exome AF: 0.870

Gnomad NFE exome AF: 0.819

Gnomad OTH exome AF: 0.805

GnomAD4 exome AF: 0.807 AC: 1177329 AN: 1459134 Hom.: 476634 Cov.: 40 AF XY: 0.806 AC XY: 585307 AN XY: 726074

African (AFR) AF: 0.589 AC: 19683 AN: 33432

American (AMR) AF: 0.826 AC: 36937 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 20439 AN: 26124

East Asian (EAS) AF: 0.806 AC: 31994 AN: 39692

South Asian (SAS) AF: 0.730 AC: 62886 AN: 86192

European-Finnish (FIN) AF: 0.869 AC: 46393 AN: 53388

Middle Eastern (MID) AF: 0.781 AC: 4502 AN: 5762

European-Non Finnish (NFE) AF: 0.817 AC: 906479 AN: 1109546

Other (OTH) AF: 0.797 AC: 48016 AN: 60276

GnomAD4 genome AF: 0.759 AC: 115485 AN: 152120 Hom.: 44637 Cov.: 33 AF XY: 0.764 AC XY: 56820 AN XY: 74404

African (AFR) AF: 0.598 AC: 24819 AN: 41484

American (AMR) AF: 0.798 AC: 12198 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2709 AN: 3472

East Asian (EAS) AF: 0.821 AC: 4243 AN: 5166

South Asian (SAS) AF: 0.719 AC: 3471 AN: 4826

European-Finnish (FIN) AF: 0.875 AC: 9273 AN: 10602

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56159 AN: 67966

Other (OTH) AF: 0.787 AC: 1664 AN: 2114

Alfa AF: 0.758 Hom.: 26733

Bravo AF: 0.747

Asia WGS AF: 0.749 AC: 2607 AN: 3478

EpiCase AF: 0.820

EpiControl AF: 0.823

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Platelet-type bleeding disorder 11 Benign:1

Aug 10, 2021

Genome-Nilou Lab

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.73
PhyloP100		-0.046
Mutation Taster		=100/0	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: rs892089; hg19: chr19-55539061; COSMIC: COSV59978923;