Variant 19-55014156-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001083899.2(GP6):c.1789A>C(p.Thr597Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 700,030 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 57 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 33 hom. )

Consequence

GP6
NM_001083899.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.748

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:):

GP6-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032471418).

BP6

Variant 19-55014156-T-G is Benign according to our data. Variant chr19-55014156-T-G is described in ClinVar as [Benign]. Clinvar id is 2126723.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2037/152140) while in subpopulation AFR AF= 0.046 (1910/41482). AF 95% confidence interval is 0.0443. There are 57 homozygotes in gnomad4. There are 926 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GP6	NM_001083899.2 linkuse as main transcript	c.1789A>C	p.Thr597Pro	missense_variant	8/8	ENST00000310373.7	NP_001077368.2	Q9HCN6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7 linkuse as main transcript	c.1789A>C	p.Thr597Pro	missense_variant	8/8	1	NM_001083899.2	ENSP00000308782.3		Q9HCN6-3
GP6	ENST00000417454 linkuse as main transcript	c.*765A>C		3_prime_UTR_variant	8/8	1		ENSP00000394922.1		Q9HCN6-1

Frequencies

GnomAD3 genomes

AF:

0.0134

AC:

2037

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0462

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00911

GnomAD3 exomes

AF:

0.00286

AC:

380

AN:

132898

Hom.:

AF XY:

0.00233

AC XY:

168

AN XY:

72186

show subpopulations

Gnomad AFR exome

AF:

0.0478

Gnomad AMR exome

AF:

0.00208

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000880

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000396

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.00183

AC:

1004

AN:

547890

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

417

AN XY:

296818

show subpopulations

Gnomad4 AFR exome

AF:

0.0480

Gnomad4 AMR exome

AF:

0.00297

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000966

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000571

Gnomad4 OTH exome

AF:

0.00368

GnomAD4 genome

AF:

0.0134

AC:

2037

AN:

152140

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

926

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0460

Gnomad4 AMR

AF:

0.00654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00901

Alfa

AF:

0.00214

Hom.:

Bravo

AF:

0.0157

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0253

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00184

AC:

182

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.60

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.88

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.30

REVEL

Benign

0.063

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

0.89

Vest4

0.20

MVP

0.085

MPC

0.57

ClinPred

0.072

GERP RS

-0.47

gMVP

0.11

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