chr19-55018667-C-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.709G>A(p.Glu237Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,598,796 control chromosomes in the GnomAD database, including 529,133 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 46051 hom., cov: 33)

Exomes 𝑓: 0.82 ( 483082 hom. )

Consequence

GP6
NM_016363.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.136

Publications

50 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=9.058281E-7).

BP6

Variant 19-55018667-C-T is Benign according to our data. Variant chr19-55018667-C-T is described in ClinVar as Benign. ClinVar VariationId is 257423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.83 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	UniProt
GP6	NM_016363.5	MANE Select	c.709G>A	p.Glu237Lys	missense	Exon 6 of 8	NP_057447.5	Q9HCN6-1
GP6	NM_001083899.2		c.709G>A	p.Glu237Lys	missense	Exon 6 of 8	NP_001077368.2	Q9HCN6-3
GP6	NM_001256017.2		c.655G>A	p.Glu219Lys	missense	Exon 5 of 7	NP_001242946.2	Q9HCN6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GP6	ENST00000417454.5	TSL:1 MANE Select	c.709G>A	p.Glu237Lys	missense	Exon 6 of 8	ENSP00000394922.1	Q9HCN6-1
GP6	ENST00000310373.7	TSL:1	c.709G>A	p.Glu237Lys	missense	Exon 6 of 8	ENSP00000308782.3	Q9HCN6-3
GP6	ENST00000333884.2	TSL:1	c.655G>A	p.Glu219Lys	missense	Exon 5 of 7	ENSP00000334552.2	Q9HCN6-2

Frequencies

GnomAD3 genomes

AF:

0.772

AC:

117437

AN:

152052

Hom.:

46044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.623

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.810

Gnomad ASJ

AF:

0.796

Gnomad EAS

AF:

0.822

Gnomad SAS

AF:

0.722

Gnomad FIN

AF:

0.877

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.836

Gnomad OTH

AF:

0.804

GnomAD2 exomes

AF:

0.807

AC:

201296

AN:

249554

AF XY:

0.805

show subpopulations

Gnomad AFR exome

AF:

0.609

Gnomad AMR exome

AF:

0.837

Gnomad ASJ exome

AF:

0.800

Gnomad EAS exome

AF:

0.834

Gnomad FIN exome

AF:

0.872

Gnomad NFE exome

AF:

0.829

Gnomad OTH exome

AF:

0.815

GnomAD4 exome

AF:

0.816

AC:

1180211

AN:

1446626

Hom.:

483082

Cov.:

AF XY:

0.815

AC XY:

587177

AN XY:

720582

show subpopulations

African (AFR)

AF:

0.611

AC:

20294

AN:

33188

American (AMR)

AF:

0.833

AC:

37250

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.798

AC:

20770

AN:

26026

East Asian (EAS)

AF:

0.806

AC:

31934

AN:

39642

South Asian (SAS)

AF:

0.732

AC:

62929

AN:

85928

European-Finnish (FIN)

AF:

0.872

AC:

46559

AN:

53420

Middle Eastern (MID)

AF:

0.786

AC:

4514

AN:

5746

European-Non Finnish (NFE)

AF:

0.827

AC:

907765

AN:

1098132

Other (OTH)

AF:

0.805

AC:

48196

AN:

59834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

10423

20845

31268

41690

52113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20594

41188

61782

82376

102970

<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:

0.772

AC:

117487

AN:

152170

Hom.:

46051

Cov.:

AF XY:

0.776

AC XY:

57734

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.623

AC:

25817

AN:

41460

American (AMR)

AF:

0.810

AC:

12380

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.796

AC:

2763

AN:

3470

East Asian (EAS)

AF:

0.821

AC:

4254

AN:

5184

South Asian (SAS)

AF:

0.722

AC:

3488

AN:

4834

European-Finnish (FIN)

AF:

0.877

AC:

9296

AN:

10604

Middle Eastern (MID)

AF:

0.847

AC:

249

AN:

294

European-Non Finnish (NFE)

AF:

0.836

AC:

56842

AN:

68006

Other (OTH)

AF:

0.802

AC:

1696

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1355

2711

4066

5422

6777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<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:

0.777

Hom.:

38370

Bravo

AF:

0.761

TwinsUK

AF:

0.825

AC:

3058

ALSPAC

AF:

0.820

AC:

3162

ESP6500AA

AF:

0.625

AC:

2441

ESP6500EA

AF:

0.833

AC:

6911

ExAC

AF:

0.800

AC:

96713

Asia WGS

AF:

0.750

AC:

2610

AN:

3478

EpiCase

AF:

0.830

EpiControl

AF:

0.832

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Platelet-type bleeding disorder 11 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.1

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.019

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0023

MetaRNN

Benign

9.1e-7

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.4

PhyloP100

-0.14

PrimateAI

Benign

0.33

PROVEAN

Benign

0.58

REVEL

Benign

0.0070

Sift

Benign

0.79

Sift4G

Benign

0.95

Polyphen

0.0

Vest4

0.13

MPC

0.19

ClinPred

0.00050

GERP RS

-1.8

Varity_R

0.028

gMVP

0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

Other links and lift over