rs1654419

Variant names:

• chr19-55024513-A-G
• rs1654419
• NM_016363.5:c.664+705T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016363.5(GP6):​c.664+705T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,078 control chromosomes in the GnomAD database, including 44,868 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44868 hom., cov: 31)
• Consequence: GP6 NM_016363.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 13 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]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP6	NM_016363.5	c.664+705T>C		intron_variant	Intron 5 of 7	ENST00000417454.5	NP_057447.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000417454.5	c.664+705T>C		intron_variant	Intron 5 of 7	1	NM_016363.5	ENSP00000394922.1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115796 AN: 151960 Hom.: 44857 Cov.: 31

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.790

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.762 AC: 115854 AN: 152078 Hom.: 44868 Cov.: 31 AF XY: 0.766 AC XY: 56971 AN XY: 74342

African (AFR) AF: 0.609 AC: 25223 AN: 41442

American (AMR) AF: 0.797 AC: 12170 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2707 AN: 3470

East Asian (EAS) AF: 0.821 AC: 4250 AN: 5176

South Asian (SAS) AF: 0.719 AC: 3464 AN: 4816

European-Finnish (FIN) AF: 0.874 AC: 9248 AN: 10580

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56177 AN: 68008

Other (OTH) AF: 0.788 AC: 1665 AN: 2114

Alfa AF: 0.728 Hom.: 10773

Bravo AF: 0.750

Asia WGS AF: 0.749 AC: 2607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.3
DANN	Benign	0.41
PhyloP100		-0.084
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.98
Mutation Taster		=100/0	polymorphism (auto)

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: rs1654419; hg19: chr19-55535881;