chr19-55014129-A-G

Position:

• chr19-55014129-A-G

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.1816T>C​(p.Phe606Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 690,984 control chromosomes in the GnomAD database, including 221,911 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 0.75 (44359 hom., cov: 31)
  • Exomes 𝑓: 0.81 (177552 hom.)
• Consequence: GP6 NM_001083899.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.84

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-AS1 (HGNC:55305): (GP6 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0786426E-6).
• BP6: Variant 19-55014129-A-G is Benign according to our data. Variant chr19-55014129-A-G is described in ClinVar as [Benign]. Clinvar id is 257416.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.1816T>C	p.Phe606Leu	missense_variant	8/8	ENST00000310373.7	NP_001077368.2
GP6-AS1	XR_001754012.3	n.121+7665A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7	c.1816T>C	p.Phe606Leu	missense_variant	8/8	1	NM_001083899.2	ENSP00000308782
GP6-AS1	ENST00000593060.5	n.155+7665A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114725 AN: 151914 Hom.: 44351 Cov.: 31

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.789

GnomAD3 exomes AF: 0.798 AC: 103813 AN: 130156 Hom.: 41873 AF XY: 0.795 AC XY: 56306 AN XY: 70860

Gnomad AFR exome AF: 0.563

Gnomad AMR exome AF: 0.830

Gnomad ASJ exome AF: 0.794

Gnomad EAS exome AF: 0.837

Gnomad SAS exome AF: 0.733

Gnomad FIN exome AF: 0.870

Gnomad NFE exome AF: 0.825

Gnomad OTH exome AF: 0.808

GnomAD4 exome AF: 0.809 AC: 435962 AN: 538952 Hom.: 177552 Cov.: 3 AF XY: 0.807 AC XY: 235572 AN XY: 292034

Gnomad4 AFR exome AF: 0.564

Gnomad4 AMR exome AF: 0.825

Gnomad4 ASJ exome AF: 0.797

Gnomad4 EAS exome AF: 0.805

Gnomad4 SAS exome AF: 0.733

Gnomad4 FIN exome AF: 0.872

Gnomad4 NFE exome AF: 0.830

Gnomad4 OTH exome AF: 0.799

GnomAD4 genome AF: 0.755 AC: 114778 AN: 152032 Hom.: 44359 Cov.: 31 AF XY: 0.758 AC XY: 56358 AN XY: 74306

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.792

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.876

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.786

Alfa AF: 0.812 Hom.: 41537

Bravo AF: 0.742

TwinsUK AF: 0.821 AC: 3045

ALSPAC AF: 0.817 AC: 3149

ESP6500AA AF: 0.677 AC: 2061

ESP6500EA AF: 0.870 AC: 5295

ExAC AF: 0.699 AC: 35526

Asia WGS AF: 0.751 AC: 2612 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.95
DANN	Benign	0.087
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00094	N
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.028
Sift	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.013
MutPred		0.18		Gain of disorder (P = 0.1036);
MPC		0.19
ClinPred		0.00014	T
GERP RS		-0.47
gMVP		0.013

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: rs1671150; hg19: chr19-55525497;