rs5030705

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000310373.7(GP6):​c.507G>A​(p.Thr169=) 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
ENST00000310373.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.85
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GP6NM_001083899.2 linkuse as main transcriptc.507G>A p.Thr169= synonymous_variant 4/8 ENST00000310373.7 NP_001077368.2
GP6-AS1XR_001754012.3 linkuse as main transcriptn.122-15119C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GP6ENST00000310373.7 linkuse as main transcriptc.507G>A p.Thr169= synonymous_variant 4/81 NM_001083899.2 ENSP00000308782 Q9HCN6-3
GP6-AS1ENST00000593060.5 linkuse as main transcriptn.156-15119C>T intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.146
AC:
22215
AN:
152118
Hom.:
2270
Cov.:
34
show subpopulations
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
GnomAD3 exomes
AF:
0.148
AC:
36815
AN:
249498
Hom.:
3600
AF XY:
0.148
AC XY:
20026
AN XY:
135390
show subpopulations
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 SAS exome
AF:
0.0602
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0350
Gnomad4 AMR exome
AF:
0.0907
Gnomad4 ASJ exome
AF:
0.0999
Gnomad4 EAS exome
AF:
0.0368
Gnomad4 SAS exome
AF:
0.0613
Gnomad4 FIN exome
AF:
0.244
Gnomad4 NFE exome
AF:
0.219
Gnomad4 OTH exome
AF:
0.164
GnomAD4 genome
AF:
0.146
AC:
22205
AN:
152236
Hom.:
2270
Cov.:
34
AF XY:
0.145
AC XY:
10774
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.0409
Gnomad4 AMR
AF:
0.127
Gnomad4 ASJ
AF:
0.0976
Gnomad4 EAS
AF:
0.0263
Gnomad4 SAS
AF:
0.0516
Gnomad4 FIN
AF:
0.236
Gnomad4 NFE
AF:
0.218
Gnomad4 OTH
AF:
0.144
Alfa
AF:
0.183
Hom.:
1436
Bravo
AF:
0.132
Asia WGS
AF:
0.0430
AC:
150
AN:
3478
EpiCase
AF:
0.198
EpiControl
AF:
0.202

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingGeneDxJun 09, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
0.088
DANN
Benign
0.92

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs5030705; hg19: chr19-55539049; COSMIC: COSV59976388; API