rs5030705

Variant names:

• chr19-55027681-C-T
• rs5030705
• NM_016363.5:c.507G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001083899.2(GP6):​c.507G>A​(p.Thr169Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,611,158 control chromosomes in the GnomAD database, including 32,180 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2270 hom., cov: 34)
  • Exomes 𝑓: 0.19 (29910 hom.)
• Consequence: GP6 NM_001083899.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.85
• 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]

ENSG00000267149 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-55027681-C-T is Benign according to our data. Variant chr19-55027681-C-T is described in ClinVar as Benign. ClinVar VariationId is 257420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.85 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083899.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	NM_016363.5	MANE Select	c.507G>A	p.Thr169Thr	synonymous	Exon 4 of 8	NP_057447.5
	GP6	NM_001083899.2		c.507G>A	p.Thr169Thr	synonymous	Exon 4 of 8	NP_001077368.2
	GP6	NM_001256017.2		c.507G>A	p.Thr169Thr	synonymous	Exon 4 of 7	NP_001242946.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	ENST00000417454.5	TSL:1 MANE Select	c.507G>A	p.Thr169Thr	synonymous	Exon 4 of 8	ENSP00000394922.1
	GP6	ENST00000310373.7	TSL:1	c.507G>A	p.Thr169Thr	synonymous	Exon 4 of 8	ENSP00000308782.3
	GP6	ENST00000333884.2	TSL:1	c.507G>A	p.Thr169Thr	synonymous	Exon 4 of 7	ENSP00000334552.2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22215 AN: 152118 Hom.: 2270 Cov.: 34

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0976

Gnomad EAS AF: 0.0268

Gnomad SAS AF: 0.0515

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.146

GnomAD2 exomes AF: 0.148 AC: 36815 AN: 249498 AF XY: 0.148

Gnomad AFR exome AF: 0.0377

Gnomad AMR exome AF: 0.0867

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.0262

Gnomad FIN exome AF: 0.248

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.192 AC: 280838 AN: 1458922 Hom.: 29910 Cov.: 39 AF XY: 0.189 AC XY: 137384 AN XY: 726042

African (AFR) AF: 0.0350 AC: 1172 AN: 33456

American (AMR) AF: 0.0907 AC: 4057 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0999 AC: 2609 AN: 26128

East Asian (EAS) AF: 0.0368 AC: 1461 AN: 39684

South Asian (SAS) AF: 0.0613 AC: 5288 AN: 86222

European-Finnish (FIN) AF: 0.244 AC: 12997 AN: 53374

Middle Eastern (MID) AF: 0.0889 AC: 512 AN: 5762

European-Non Finnish (NFE) AF: 0.219 AC: 242834 AN: 1109292

Other (OTH) AF: 0.164 AC: 9908 AN: 60282

GnomAD4 genome AF: 0.146 AC: 22205 AN: 152236 Hom.: 2270 Cov.: 34 AF XY: 0.145 AC XY: 10774 AN XY: 74424

African (AFR) AF: 0.0409 AC: 1699 AN: 41558

American (AMR) AF: 0.127 AC: 1938 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0976 AC: 339 AN: 3472

East Asian (EAS) AF: 0.0263 AC: 136 AN: 5174

South Asian (SAS) AF: 0.0516 AC: 249 AN: 4830

European-Finnish (FIN) AF: 0.236 AC: 2497 AN: 10594

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14803 AN: 67996

Other (OTH) AF: 0.144 AC: 303 AN: 2110

Alfa AF: 0.182 Hom.: 1440

Bravo AF: 0.132

Asia WGS AF: 0.0430 AC: 150 AN: 3478

EpiCase AF: 0.198

EpiControl AF: 0.202

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.088
DANN	Benign	0.92
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5030705; hg19: chr19-55539049; COSMIC: COSV59976388;