rs892089

chr19-55027693-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001083899.2(GP6):c.495T>C(p.Phe165=) 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:4
• Conservation: PhyloP100: -0.0460

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]

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

ACMG classification

Verdict is Benign. Variant got -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 id is 257419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55027693-A-G is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
GP6	NM_001083899.2	c.495T>C	p.Phe165=	synonymous_variant	4/8	ENST00000310373.7
GP6-AS1	XR_001754012.3	n.122-15107A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GP6	ENST00000310373.7	c.495T>C	p.Phe165=	synonymous_variant	4/8	1	NM_001083899.2
GP6-AS1	ENST00000593060.5	n.156-15107A>G		intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes AF: 0.799 AC: 199303 AN: 249510 Hom.: 80307 AF XY: 0.798 AC XY: 107976 AN XY: 135390

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 SAS exome AF: 0.725

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

Gnomad4 AFR exome AF: 0.589

Gnomad4 AMR exome AF: 0.826

Gnomad4 ASJ exome AF: 0.782

Gnomad4 EAS exome AF: 0.806

Gnomad4 SAS exome AF: 0.730

Gnomad4 FIN exome AF: 0.869

Gnomad4 NFE exome AF: 0.817

Gnomad4 OTH exome AF: 0.797

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

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.798

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.875

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.787

Alfa AF: 0.789 Hom.: 22809

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Platelet-type bleeding disorder 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.9
Dann	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs892089; hg19: chr19-55539061; COSMIC: COSV59978923;