19-55014450-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 12/17 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

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 made for transcript

Verdict is Benign. Variant got -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 id is 257412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55014450-C-T is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

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 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

GnomAD3 exomes

AF:

0.0245

AC:

6105

AN:

249568

Hom.:

108

AF XY:

0.0249

AC XY:

3367

AN XY:

135402

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 SAS exome

AF:

0.00572

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

Gnomad4 AFR exome

AF:

0.00400

Gnomad4 AMR exome

AF:

0.0204

Gnomad4 ASJ exome

AF:

0.0408

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.00617

Gnomad4 FIN exome

AF:

0.0377

Gnomad4 NFE exome

AF:

0.0310

Gnomad4 OTH exome

AF:

0.0266

GnomAD4 genome

AF:

0.0231

AC:

3512

AN:

152222

Hom.:

Cov.:

AF XY:

0.0232

AC XY:

1729

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00575

Gnomad4 AMR

AF:

0.0221

Gnomad4 ASJ

AF:

0.0409

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.0425

Gnomad4 NFE

AF:

0.0327

Gnomad4 OTH

AF:

0.0285

Alfa

AF:

0.0316

Hom.:

150

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

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

- -

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

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.40

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over