19-55014991-A-T

Variant names:

Variant summary

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

The NM_016363.5(GP6):c.950T>A(p.Leu317Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 1,611,472 control chromosomes in the GnomAD database, including 525,516 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43922 hom., cov: 32)

Exomes 𝑓: 0.81 ( 481594 hom. )

Consequence

GP6
NM_016363.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.855

Publications

36 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=8.496274E-7).

BP6

Variant 19-55014991-A-T is Benign according to our data. Variant chr19-55014991-A-T is described in ClinVar as Benign. ClinVar VariationId is 257427.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.950T>A	p.Leu317Gln	missense_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.950T>A	p.Leu317Gln	missense_variant	Exon 8 of 8	1	NM_016363.5	ENSP00000394922.1

Frequencies

GnomAD3 genomes

AF:

0.752

AC:

113947

AN:

151600

Hom.:

43915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.559

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.801

Gnomad ASJ

AF:

0.792

Gnomad EAS

AF:

0.823

Gnomad SAS

AF:

0.721

Gnomad FIN

AF:

0.875

Gnomad MID

AF:

0.841

Gnomad NFE

AF:

0.831

Gnomad OTH

AF:

0.788

GnomAD2 exomes

AF:

0.801

AC:

196210

AN:

245108

AF XY:

0.799

show subpopulations

Gnomad AFR exome

AF:

0.548

Gnomad AMR exome

AF:

0.833

Gnomad ASJ exome

AF:

0.799

Gnomad EAS exome

AF:

0.836

Gnomad FIN exome

AF:

0.870

Gnomad NFE exome

AF:

0.825

Gnomad OTH exome

AF:

0.811

GnomAD4 exome

AF:

0.811

AC:

1183492

AN:

1459754

Hom.:

481594

Cov.:

AF XY:

0.810

AC XY:

588117

AN XY:

726126

show subpopulations

African (AFR)

AF:

0.549

AC:

18333

AN:

33400

American (AMR)

AF:

0.828

AC:

36936

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.795

AC:

20767

AN:

26108

East Asian (EAS)

AF:

0.809

AC:

32066

AN:

39642

South Asian (SAS)

AF:

0.732

AC:

63006

AN:

86044

European-Finnish (FIN)

AF:

0.871

AC:

46225

AN:

53068

Middle Eastern (MID)

AF:

0.782

AC:

4508

AN:

5762

European-Non Finnish (NFE)

AF:

0.822

AC:

913438

AN:

1110808

Other (OTH)

AF:

0.799

AC:

48213

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

11767

23533

35300

47066

58833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20886

41772

62658

83544

104430

<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:

0.751

AC:

113999

AN:

151718

Hom.:

43922

Cov.:

AF XY:

0.755

AC XY:

55954

AN XY:

74120

show subpopulations

African (AFR)

AF:

0.559

AC:

23100

AN:

41336

American (AMR)

AF:

0.801

AC:

12225

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.792

AC:

2746

AN:

3468

East Asian (EAS)

AF:

0.822

AC:

4242

AN:

5160

South Asian (SAS)

AF:

0.722

AC:

3479

AN:

4820

European-Finnish (FIN)

AF:

0.875

AC:

9222

AN:

10538

Middle Eastern (MID)

AF:

0.839

AC:

245

AN:

292

European-Non Finnish (NFE)

AF:

0.831

AC:

56386

AN:

67824

Other (OTH)

AF:

0.786

AC:

1658

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1359

2718

4076

5435

6794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.812

Hom.:

29088

Bravo

AF:

0.738

TwinsUK

AF:

0.826

AC:

3062

ALSPAC

AF:

0.818

AC:

3152

ESP6500AA

AF:

0.559

AC:

2142

ESP6500EA

AF:

0.831

AC:

6849

ExAC

AF:

0.789

AC:

95235

Asia WGS

AF:

0.752

AC:

2615

AN:

3476

EpiCase

AF:

0.824

EpiControl

AF:

0.824

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

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

AlphaMissense

Benign

0.041

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.5

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.0

.;.

MetaRNN

Benign

8.5e-7

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;.

PhyloP100

-0.85

PROVEAN

Benign

1.6

N;N

REVEL

Benign

0.011

Sift

Benign

0.53

T;T

Sift4G

Benign

0.11

T;T

Vest4

0.035

ClinPred

0.0015

GERP RS

-0.95

Varity_R

0.070

Mutation Taster

=98/2

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