19-55027612-T-C

Variant names:

• chr19-55027612-T-C
• rs1654425
• NM_016363.5:c.576A>G

Variant summary

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

The NM_016363.5(GP6):​c.576A>G​(p.Ser192Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 1,612,182 control chromosomes in the GnomAD database, including 585,513 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60638 hom., cov: 34)
  • Exomes 𝑓: 0.85 (524875 hom.)
• Consequence: GP6 NM_016363.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -5.64
• Publications: 23 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 19-55027612-T-C is Benign according to our data. Variant chr19-55027612-T-C is described in ClinVar as Benign. ClinVar VariationId is 257421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP6	NM_016363.5	c.576A>G	p.Ser192Ser	synonymous_variant	Exon 4 of 8	ENST00000417454.5	NP_057447.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000417454.5	c.576A>G	p.Ser192Ser	synonymous_variant	Exon 4 of 8	1	NM_016363.5	ENSP00000394922.1

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135448 AN: 152148 Hom.: 60583 Cov.: 34

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.887

GnomAD2 exomes AF: 0.868 AC: 216379 AN: 249170 AF XY: 0.859

Gnomad AFR exome AF: 0.970

Gnomad AMR exome AF: 0.939

Gnomad ASJ exome AF: 0.800

Gnomad EAS exome AF: 0.983

Gnomad FIN exome AF: 0.884

Gnomad NFE exome AF: 0.840

Gnomad OTH exome AF: 0.851

GnomAD4 exome AF: 0.847 AC: 1236311 AN: 1459916 Hom.: 524875 Cov.: 45 AF XY: 0.845 AC XY: 613782 AN XY: 726390

African (AFR) AF: 0.970 AC: 32481 AN: 33470

American (AMR) AF: 0.937 AC: 41893 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 20762 AN: 26120

East Asian (EAS) AF: 0.981 AC: 38954 AN: 39692

South Asian (SAS) AF: 0.790 AC: 68092 AN: 86212

European-Finnish (FIN) AF: 0.883 AC: 47039 AN: 53292

Middle Eastern (MID) AF: 0.825 AC: 4753 AN: 5758

European-Non Finnish (NFE) AF: 0.838 AC: 930805 AN: 1110310

Other (OTH) AF: 0.854 AC: 51532 AN: 60342

GnomAD4 genome AF: 0.890 AC: 135565 AN: 152266 Hom.: 60638 Cov.: 34 AF XY: 0.892 AC XY: 66398 AN XY: 74450

African (AFR) AF: 0.966 AC: 40152 AN: 41566

American (AMR) AF: 0.913 AC: 13964 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2760 AN: 3470

East Asian (EAS) AF: 0.976 AC: 5043 AN: 5168

South Asian (SAS) AF: 0.787 AC: 3793 AN: 4822

European-Finnish (FIN) AF: 0.890 AC: 9442 AN: 10608

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.847 AC: 57584 AN: 68012

Other (OTH) AF: 0.886 AC: 1873 AN: 2114

Alfa AF: 0.860 Hom.: 93568

Bravo AF: 0.897

Asia WGS AF: 0.898 AC: 3122 AN: 3478

EpiCase AF: 0.839

EpiControl AF: 0.842

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

- -

Nov 12, 2018

GeneDx

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

- -

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	0.19
DANN	Benign	0.72
PhyloP100		-5.6
Mutation Taster		=99/1	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: rs1654425; hg19: chr19-55538980; COSMIC: COSV59978877; COSMIC: COSV59978877;