Genetic Variant GP6:p.Phe165Phe (chr19-55027693-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016363.5(GP6):c.495T>C(p.Phe165Phe) 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_016363.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0460

Publications

19 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:

ENSG00000267149 (HGNC:):

ENSG00000267149 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 -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 VariationId is 257419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016363.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GP6	NM_016363.5	MANE Select	c.495T>C	p.Phe165Phe	synonymous	Exon 4 of 8	NP_057447.5
GP6	NM_001083899.2		c.495T>C	p.Phe165Phe	synonymous	Exon 4 of 8	NP_001077368.2
GP6	NM_001256017.2		c.495T>C	p.Phe165Phe	synonymous	Exon 4 of 7	NP_001242946.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GP6	ENST00000417454.5	TSL:1 MANE Select	c.495T>C	p.Phe165Phe	synonymous	Exon 4 of 8	ENSP00000394922.1
GP6	ENST00000310373.7	TSL:1	c.495T>C	p.Phe165Phe	synonymous	Exon 4 of 8	ENSP00000308782.3
GP6	ENST00000333884.2	TSL:1	c.495T>C	p.Phe165Phe	synonymous	Exon 4 of 7	ENSP00000334552.2

Frequencies

GnomAD3 genomes

AF:

0.759

AC:

115429

AN:

152002

Hom.:

44627

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.799

AC:

199303

AN:

249510

AF XY:

0.798

show subpopulations

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 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.:

AF XY:

0.806

AC XY:

585307

AN XY:

726074

show subpopulations

African (AFR)

AF:

0.589

AC:

19683

AN:

33432

American (AMR)

AF:

0.826

AC:

36937

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.782

AC:

20439

AN:

26124

East Asian (EAS)

AF:

0.806

AC:

31994

AN:

39692

South Asian (SAS)

AF:

0.730

AC:

62886

AN:

86192

European-Finnish (FIN)

AF:

0.869

AC:

46393

AN:

53388

Middle Eastern (MID)

AF:

0.781

AC:

4502

AN:

5762

European-Non Finnish (NFE)

AF:

0.817

AC:

906479

AN:

1109546

Other (OTH)

AF:

0.797

AC:

48016

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

12026

24052

36077

48103

60129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20808

41616

62424

83232

104040

<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:

0.759

AC:

115485

AN:

152120

Hom.:

44637

Cov.:

AF XY:

0.764

AC XY:

56820

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.598

AC:

24819

AN:

41484

American (AMR)

AF:

0.798

AC:

12198

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.780

AC:

2709

AN:

3472

East Asian (EAS)

AF:

0.821

AC:

4243

AN:

5166

South Asian (SAS)

AF:

0.719

AC:

3471

AN:

4826

European-Finnish (FIN)

AF:

0.875

AC:

9273

AN:

10602

Middle Eastern (MID)

AF:

0.844

AC:

248

AN:

294

European-Non Finnish (NFE)

AF:

0.826

AC:

56159

AN:

67966

Other (OTH)

AF:

0.787

AC:

1664

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1403

2807

4210

5614

7017

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

854

1708

2562

3416

4270

<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:

0.758

Hom.:

26733

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: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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.9

(source)

DANN

Benign

0.73

PhyloP100

-0.046

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over