rs892090

Variant names:

• chr19-55027704-T-A
• rs892090
• NM_001083899.2:c.484A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-55027704-T-A
• chr19-55027704-T-C
• chr19-55027704-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001083899.2(GP6):​c.484A>T​(p.Arg162Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000789 in 152,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R162R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GP6 NM_001083899.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 25 publications found

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]

ENSG00000267149 (HGNC:):

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12568304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP6	NM_001083899.2	c.484A>T	p.Arg162Trp	missense_variant	Exon 4 of 8	ENST00000310373.7	NP_001077368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7	c.484A>T	p.Arg162Trp	missense_variant	Exon 4 of 8	1	NM_001083899.2	ENSP00000308782.3
GP6	ENST00000417454.5	c.484A>T	p.Arg162Trp	missense_variant	Exon 4 of 8	1		ENSP00000394922.1

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152108 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00000801 AC: 2 AN: 249534 AF XY: 0.0000148

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000548 AC: 8 AN: 1460788 Hom.: 0 Cov.: 43 AF XY: 0.00000550 AC XY: 4 AN XY: 726768

African (AFR) AF: 0.000120 AC: 4 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111022

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152108 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74310

African (AFR) AF: 0.000266 AC: 11 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00 Hom.: 109260

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.17	T;.;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.016	N
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.42	N;N;N;.
PhyloP100		0.19
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.5	D;D;D;.
REVEL	Benign	0.015
Sift	Benign	0.16	T;D;T;.
Sift4G	Benign	0.22	T;T;T;.
Polyphen		0.015	B;B;B;.
Vest4		0.16
MutPred		0.65		Loss of catalytic residue at R162 (P = 0.0552);Loss of catalytic residue at R162 (P = 0.0552);Loss of catalytic residue at R162 (P = 0.0552);.;
MVP		0.16
MPC		0.19
ClinPred		0.13	T
GERP RS		0.57
Varity_R		0.21
gMVP		0.43
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs892090; hg19: chr19-55539072;