rs1654419

chr19-55024513-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001083899.2(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_001083899.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840

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 -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/exons	MANE	UniProt
GP6	NM_001083899.2	c.664+705T>C		intron_variant		ENST00000310373.7
GP6-AS1	XR_001754012.3	n.121+18049A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GP6	ENST00000310373.7	c.664+705T>C		intron_variant		1	NM_001083899.2
GP6-AS1	ENST00000593060.5	n.155+18049A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.797

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.874

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.788

Alfa AF: 0.791 Hom.: 7639

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.98

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: rs1654419; hg19: chr19-55535881;