19-55015005-G-C

Position:

chr19-55015005-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000310373.7(GP6):c.940C>G(p.Pro314Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,900 control chromosomes in the GnomAD database, including 19,636 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P314P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.48 ( 19636 hom., cov: 33)

Exomes 𝑓: 0.57 ( 241399 hom. )

Failed GnomAD Quality Control

Consequence

GP6
ENST00000310373.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.277

Variant links:

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 links:

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

GP6-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.248344E-5).

BP6

Variant 19-55015005-G-C is Benign according to our data. Variant chr19-55015005-G-C is described in ClinVar as [Benign]. Clinvar id is 257426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55015005-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GP6	NM_001083899.2 linkuse as main transcript	c.940C>G	p.Pro314Ala	missense_variant	8/8	ENST00000310373.7	NP_001077368.2
GP6-AS1	XR_001754012.3 linkuse as main transcript	n.121+8541G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7 linkuse as main transcript	c.940C>G	p.Pro314Ala	missense_variant	8/8	1	NM_001083899.2	ENSP00000308782		Q9HCN6-3
GP6-AS1	ENST00000593060.5 linkuse as main transcript	n.155+8541G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.482

AC:

73233

AN:

151784

Hom.:

19644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.547

Gnomad EAS

AF:

0.236

Gnomad SAS

AF:

0.438

Gnomad FIN

AF:

0.628

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.604

Gnomad OTH

AF:

0.507

GnomAD3 exomes

AF:

0.520

AC:

126039

AN:

242548

Hom.:

34560

AF XY:

0.525

AC XY:

69394

AN XY:

132098

show subpopulations

Gnomad AFR exome

AF:

0.245

Gnomad AMR exome

AF:

0.489

Gnomad ASJ exome

AF:

0.548

Gnomad EAS exome

AF:

0.235

Gnomad SAS exome

AF:

0.465

Gnomad FIN exome

AF:

0.623

Gnomad NFE exome

AF:

0.602

Gnomad OTH exome

AF:

0.558

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.569

AC:

829184

AN:

1458520

Hom.:

241399

Cov.:

AF XY:

0.567

AC XY:

411367

AN XY:

725506

show subpopulations

Gnomad4 AFR exome

AF:

0.244

Gnomad4 AMR exome

AF:

0.496

Gnomad4 ASJ exome

AF:

0.539

Gnomad4 EAS exome

AF:

0.252

Gnomad4 SAS exome

AF:

0.463

Gnomad4 FIN exome

AF:

0.622

Gnomad4 NFE exome

AF:

0.600

Gnomad4 OTH exome

AF:

0.541

GnomAD4 genome

AF:

0.482

AC:

73245

AN:

151900

Hom.:

19636

Cov.:

AF XY:

0.483

AC XY:

35857

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.531

Gnomad4 ASJ

AF:

0.547

Gnomad4 EAS

AF:

0.234

Gnomad4 SAS

AF:

0.438

Gnomad4 FIN

AF:

0.628

Gnomad4 NFE

AF:

0.604

Gnomad4 OTH

AF:

0.504

Alfa

AF:

0.566

Hom.:

7576

Bravo

AF:

0.466

TwinsUK

AF:

0.599

AC:

2221

ALSPAC

AF:

0.596

AC:

2296

ESP6500AA

AF:

0.241

AC:

916

ESP6500EA

AF:

0.601

AC:

4939

ExAC

AF:

0.511

AC:

61627

Asia WGS

AF:

0.367

AC:

1278

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

GP6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 27, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Platelet-type bleeding disorder 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

0.084

Eigen_PC

Benign

-0.063

FATHMM_MKL

Benign

0.54

MetaRNN

Benign

0.000052

MetaSVM

Benign

-1.2

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.3

REVEL

Benign

0.098

Sift

Benign

0.34

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.18

MPC

0.61

ClinPred

0.022

GERP RS

2.6

gMVP

0.041

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

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