19-55014450-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001083899.2(GP6):c.1495G>A(p.Gly499Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 1,613,282 control chromosomes in the GnomAD database, including 744 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 (★★).

Frequency

Genomes: 𝑓 0.023 ( 60 hom., cov: 33)

Exomes 𝑓: 0.028 ( 684 hom. )

Consequence

GP6
NM_001083899.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0460

Publications

14 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=0.0024445355).

BP6

Variant 19-55014450-C-T is Benign according to our data. Variant chr19-55014450-C-T is described in ClinVar as Benign. ClinVar VariationId is 257412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0231 (3512/152222) while in subpopulation NFE AF = 0.0327 (2224/68012). AF 95% confidence interval is 0.0316. There are 60 homozygotes in GnomAd4. There are 1729 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP6	NM_001083899.2 link	c.1495G>A	p.Gly499Ser	missense_variant	Exon 8 of 8	ENST00000310373.7	NP_001077368.2	Q9HCN6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7 link	c.1495G>A	p.Gly499Ser	missense_variant	Exon 8 of 8	1	NM_001083899.2	ENSP00000308782.3		Q9HCN6-3
GP6	ENST00000417454.5 link	c.*471G>A		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000394922.1		Q9HCN6-1

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3511

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00577

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0222

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.0425

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0327

Gnomad OTH

AF:

0.0274

GnomAD2 exomes

AF:

0.0245

AC:

6105

AN:

249568

AF XY:

0.0249

show subpopulations

Gnomad AFR exome

AF:

0.00446

Gnomad AMR exome

AF:

0.0194

Gnomad ASJ exome

AF:

0.0416

Gnomad EAS exome

AF:

0.000278

Gnomad FIN exome

AF:

0.0368

Gnomad NFE exome

AF:

0.0335

Gnomad OTH exome

AF:

0.0292

GnomAD4 exome

AF:

0.0280

AC:

40873

AN:

1461060

Hom.:

684

Cov.:

AF XY:

0.0276

AC XY:

20071

AN XY:

726906

show subpopulations

African (AFR)

AF:

0.00400

AC:

134

AN:

33470

American (AMR)

AF:

0.0204

AC:

914

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0408

AC:

1065

AN:

26134

East Asian (EAS)

AF:

0.000252

AC:

AN:

39690

South Asian (SAS)

AF:

0.00617

AC:

532

AN:

86244

European-Finnish (FIN)

AF:

0.0377

AC:

2014

AN:

53420

Middle Eastern (MID)

AF:

0.0191

AC:

110

AN:

5766

European-Non Finnish (NFE)

AF:

0.0310

AC:

34489

AN:

1111248

Other (OTH)

AF:

0.0266

AC:

1605

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

2178

4356

6534

8712

10890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1208

2416

3624

4832

6040

<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:

0.0231

AC:

3512

AN:

152222

Hom.:

Cov.:

AF XY:

0.0232

AC XY:

1729

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00575

AC:

239

AN:

41538

American (AMR)

AF:

0.0221

AC:

338

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

142

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5186

South Asian (SAS)

AF:

0.00559

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0425

AC:

450

AN:

10600

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0327

AC:

2224

AN:

68012

Other (OTH)

AF:

0.0285

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

175

350

526

701

876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0297

Hom.:

248

Bravo

AF:

0.0220

TwinsUK

AF:

0.0254

AC:

ALSPAC

AF:

0.0296

AC:

114

ESP6500AA

AF:

0.00486

AC:

ESP6500EA

AF:

0.0346

AC:

287

ExAC

AF:

0.0250

AC:

3026

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0354

EpiControl

AF:

0.0394

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

- -

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

0.089

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.40

(source)

DANN

Benign

0.34

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0010

MetaRNN

Benign

0.0024

MetaSVM

Benign

-0.91

PhyloP100

0.046

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.41

REVEL

Benign

0.028

Sift

Pathogenic

0.0

Sift4G

Benign

0.71

Polyphen

0.0

Vest4

0.046

MPC

0.16

ClinPred

0.0051

GERP RS

0.49

gMVP

0.024

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