19-55015821-G-T

Position:

• chr19-55015821-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001083899.2(GP6):​c.725-88C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 767,388 control chromosomes in the GnomAD database, including 243,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (43186 hom., cov: 31)
  • Exomes 𝑓: 0.80 (200017 hom.)
• Consequence: GP6 NM_001083899.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.03

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-55015821-G-T is Benign according to our data. Variant chr19-55015821-G-T is described in ClinVar as [Benign]. Clinvar id is 1225054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GP6	NM_001083899.2	c.725-88C>A		intron_variant		ENST00000310373.7	NP_001077368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7	c.725-88C>A		intron_variant		1	NM_001083899.2	ENSP00000308782.3
GP6	ENST00000417454.5	c.725-88C>A		intron_variant		1		ENSP00000394922.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112584 AN: 151834 Hom.: 43182 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.782

GnomAD4 exome AF: 0.803 AC: 494099 AN: 615436 Hom.: 200017 AF XY: 0.801 AC XY: 266643 AN XY: 332716

Gnomad4 AFR exome AF: 0.512

Gnomad4 AMR exome AF: 0.820

Gnomad4 ASJ exome AF: 0.794

Gnomad4 EAS exome AF: 0.804

Gnomad4 SAS exome AF: 0.729

Gnomad4 FIN exome AF: 0.868

Gnomad4 NFE exome AF: 0.823

Gnomad4 OTH exome AF: 0.792

GnomAD4 genome AF: 0.741 AC: 112631 AN: 151952 Hom.: 43186 Cov.: 31 AF XY: 0.745 AC XY: 55316 AN XY: 74274

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.798

Gnomad4 ASJ AF: 0.792

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.876

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.780

Alfa AF: 0.774 Hom.: 6781

Bravo AF: 0.727

Asia WGS AF: 0.749 AC: 2604 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.40
DANN	Benign	0.81

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

Other links and lift over

dbSNP: rs1671153; hg19: chr19-55527189; COSMIC: COSV59978023;