19-55014228-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000310373.7(GP6):c.1717A>G(p.Arg573Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 833,636 control chromosomes in the GnomAD database, including 266,774 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: 𝑓 0.74 ( 43469 hom., cov: 31)

Exomes 𝑓: 0.81 ( 223305 hom. )

Consequence

GP6
ENST00000310373.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.833

Publications

21 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.8510706E-7).

BP6

Variant 19-55014228-T-C is Benign according to our data. Variant chr19-55014228-T-C is described in ClinVar as Benign. ClinVar VariationId is 257413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP6	NM_016363.5 link	c.*693A>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000417454.5	NP_057447.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000417454.5 link	c.*693A>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_016363.5	ENSP00000394922.1

Frequencies

GnomAD3 genomes

AF:

0.744

AC:

113073

AN:

151886

Hom.:

43463

Cov.:

show subpopulations

Gnomad AFR

AF:

0.533

Gnomad AMI

AF:

0.771

Gnomad AMR

AF:

0.799

Gnomad ASJ

AF:

0.791

Gnomad EAS

AF:

0.819

Gnomad SAS

AF:

0.721

Gnomad FIN

AF:

0.876

Gnomad MID

AF:

0.841

Gnomad NFE

AF:

0.832

Gnomad OTH

AF:

0.785

GnomAD2 exomes

AF:

0.794

AC:

157047

AN:

197690

AF XY:

0.794

show subpopulations

Gnomad AFR exome

AF:

0.520

Gnomad AMR exome

AF:

0.830

Gnomad ASJ exome

AF:

0.795

Gnomad EAS exome

AF:

0.832

Gnomad FIN exome

AF:

0.869

Gnomad NFE exome

AF:

0.824

Gnomad OTH exome

AF:

0.810

GnomAD4 exome

AF:

0.807

AC:

549800

AN:

681632

Hom.:

223305

Cov.:

AF XY:

0.805

AC XY:

294962

AN XY:

366394

show subpopulations

African (AFR)

AF:

0.526

AC:

10064

AN:

19132

American (AMR)

AF:

0.824

AC:

32684

AN:

39648

Ashkenazi Jewish (ASJ)

AF:

0.795

AC:

16731

AN:

21046

East Asian (EAS)

AF:

0.798

AC:

28532

AN:

35756

South Asian (SAS)

AF:

0.732

AC:

50175

AN:

68564

European-Finnish (FIN)

AF:

0.871

AC:

33068

AN:

37962

Middle Eastern (MID)

AF:

0.784

AC:

3280

AN:

4182

European-Non Finnish (NFE)

AF:

0.827

AC:

347259

AN:

420142

Other (OTH)

AF:

0.796

AC:

28007

AN:

35200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

6197

12394

18591

24788

30985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3248

6496

9744

12992

16240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.744

AC:

113122

AN:

152004

Hom.:

43469

Cov.:

AF XY:

0.748

AC XY:

55570

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.533

AC:

22048

AN:

41382

American (AMR)

AF:

0.799

AC:

12209

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.791

AC:

2748

AN:

3472

East Asian (EAS)

AF:

0.818

AC:

4223

AN:

5162

South Asian (SAS)

AF:

0.721

AC:

3477

AN:

4820

European-Finnish (FIN)

AF:

0.876

AC:

9274

AN:

10592

Middle Eastern (MID)

AF:

0.839

AC:

245

AN:

292

European-Non Finnish (NFE)

AF:

0.832

AC:

56548

AN:

67996

Other (OTH)

AF:

0.783

AC:

1648

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1315

2630

3946

5261

6576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.771

Hom.:

16321

Bravo

AF:

0.730

TwinsUK

AF:

0.821

AC:

3043

ALSPAC

AF:

0.817

AC:

3149

ESP6500AA

AF:

0.531

AC:

2026

ESP6500EA

AF:

0.829

AC:

6725

ExAC

AF:

0.769

AC:

90576

Asia WGS

AF:

0.746

AC:

2595

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.3

(source)

DANN

Benign

0.87

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0088

MetaRNN

Benign

8.9e-7

MetaSVM

Benign

-0.93

PhyloP100

-0.83

PrimateAI

Benign

0.44

PROVEAN

Benign

0.10

REVEL

Benign

0.060

Sift

Benign

1.0

Sift4G

Benign

0.46

Polyphen

0.60

Vest4

0.068

MPC

0.33

ClinPred

0.0029

GERP RS

-0.47

gMVP

0.022

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over