Variant 19-55027612-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001083899.2(GP6):c.576A>G(p.Ser192Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 1,612,182 control chromosomes in the GnomAD database, including 585,513 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60638 hom., cov: 34)

Exomes 𝑓: 0.85 ( 524875 hom. )

Consequence

GP6
NM_001083899.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.64

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 19-55027612-T-C is Benign according to our data. Variant chr19-55027612-T-C is described in ClinVar as [Benign]. Clinvar id is 257421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55027612-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-5.64 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GP6	NM_001083899.2 linkuse as main transcript	c.576A>G	p.Ser192Ser	synonymous_variant	4/8	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.576A>G	p.Ser192Ser	synonymous_variant	4/8	1	NM_001083899.2	ENSP00000308782.3		Q9HCN6-3
GP6	ENST00000417454.5 linkuse as main transcript	c.576A>G	p.Ser192Ser	synonymous_variant	4/8	1		ENSP00000394922.1		Q9HCN6-1

Frequencies

GnomAD3 genomes

AF:

0.890

AC:

135448

AN:

152148

Hom.:

60583

Cov.:

show subpopulations

Gnomad AFR

AF:

0.966

Gnomad AMI

AF:

0.769

Gnomad AMR

AF:

0.913

Gnomad ASJ

AF:

0.795

Gnomad EAS

AF:

0.976

Gnomad SAS

AF:

0.787

Gnomad FIN

AF:

0.890

Gnomad MID

AF:

0.864

Gnomad NFE

AF:

0.847

Gnomad OTH

AF:

0.887

GnomAD3 exomes

AF:

0.868

AC:

216379

AN:

249170

Hom.:

94555

AF XY:

0.859

AC XY:

116205

AN XY:

135250

show subpopulations

Gnomad AFR exome

AF:

0.970

Gnomad AMR exome

AF:

0.939

Gnomad ASJ exome

AF:

0.800

Gnomad EAS exome

AF:

0.983

Gnomad SAS exome

AF:

0.788

Gnomad FIN exome

AF:

0.884

Gnomad NFE exome

AF:

0.840

Gnomad OTH exome

AF:

0.851

GnomAD4 exome

AF:

0.847

AC:

1236311

AN:

1459916

Hom.:

524875

Cov.:

AF XY:

0.845

AC XY:

613782

AN XY:

726390

show subpopulations

Gnomad4 AFR exome

AF:

0.970

Gnomad4 AMR exome

AF:

0.937

Gnomad4 ASJ exome

AF:

0.795

Gnomad4 EAS exome

AF:

0.981

Gnomad4 SAS exome

AF:

0.790

Gnomad4 FIN exome

AF:

0.883

Gnomad4 NFE exome

AF:

0.838

Gnomad4 OTH exome

AF:

0.854

GnomAD4 genome

AF:

0.890

AC:

135565

AN:

152266

Hom.:

60638

Cov.:

AF XY:

0.892

AC XY:

66398

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.966

Gnomad4 AMR

AF:

0.913

Gnomad4 ASJ

AF:

0.795

Gnomad4 EAS

AF:

0.976

Gnomad4 SAS

AF:

0.787

Gnomad4 FIN

AF:

0.890

Gnomad4 NFE

AF:

0.847

Gnomad4 OTH

AF:

0.886

Alfa

AF:

0.860

Hom.:

20170

Bravo

AF:

0.897

Asia WGS

AF:

0.898

AC:

3122

AN:

3478

EpiCase

AF:

0.839

EpiControl

AF:

0.842

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Platelet-type bleeding disorder 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.19

DANN

Benign

0.72

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