19-55014228-T-G

Variant names:

• chr19-55014228-T-G
• rs1654412
• ENST00000310373.7:c.1717A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The ENST00000310373.7(GP6):​c.1717A>C​(p.Arg573Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 682,136 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: GP6 ENST00000310373.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.833
• Publications: 21 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-0.833 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP6	NM_016363.5	c.*693A>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000417454.5	NP_057447.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000417454.5	c.*693A>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_016363.5	ENSP00000394922.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000147 AC: 1 AN: 682136 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 366652

African (AFR) AF: 0.00 AC: 0 AN: 19144

American (AMR) AF: 0.00 AC: 0 AN: 39664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21056

East Asian (EAS) AF: 0.00 AC: 0 AN: 35786

South Asian (SAS) AF: 0.00 AC: 0 AN: 68574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4184

European-Non Finnish (NFE) AF: 0.00000238 AC: 1 AN: 420518

Other (OTH) AF: 0.00 AC: 0 AN: 35224

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 16321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.91
DANN	Benign	0.33
PhyloP100		-0.83

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: rs1654412; hg19: chr19-55525596;