ENST00000310373.7:c.1816T>C

Variant names:

• chr19-55014129-A-G
• rs1671150
• ENST00000310373.7:c.1816T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000310373.7(GP6):​c.1816T>C​(p.Phe606Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 690,984 control chromosomes in the GnomAD database, including 221,911 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (44359 hom., cov: 31)
  • Exomes 𝑓: 0.81 (177552 hom.)
• Consequence: GP6 ENST00000310373.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.84
• Publications: 22 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0786426E-6).
• BP6: Variant 19-55014129-A-G is Benign according to our data. Variant chr19-55014129-A-G is described in ClinVar as Benign. ClinVar VariationId is 257416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000310373.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	NM_016363.5	MANE Select	c.*792T>C		3_prime_UTR	Exon 8 of 8	NP_057447.5
	GP6	NM_001083899.2		c.1816T>C	p.Phe606Leu	missense	Exon 8 of 8	NP_001077368.2
	GP6	NM_001256017.2		c.*792T>C		3_prime_UTR	Exon 7 of 7	NP_001242946.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	ENST00000310373.7	TSL:1	c.1816T>C	p.Phe606Leu	missense	Exon 8 of 8	ENSP00000308782.3
	GP6	ENST00000417454.5	TSL:1 MANE Select	c.*792T>C		3_prime_UTR	Exon 8 of 8	ENSP00000394922.1
	GP6	ENST00000333884.2	TSL:1	c.*792T>C		3_prime_UTR	Exon 7 of 7	ENSP00000334552.2

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114725 AN: 151914 Hom.: 44351 Cov.: 31

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.789

GnomAD2 exomes AF: 0.798 AC: 103813 AN: 130156 AF XY: 0.795

Gnomad AFR exome AF: 0.563

Gnomad AMR exome AF: 0.830

Gnomad ASJ exome AF: 0.794

Gnomad EAS exome AF: 0.837

Gnomad FIN exome AF: 0.870

Gnomad NFE exome AF: 0.825

Gnomad OTH exome AF: 0.808

GnomAD4 exome AF: 0.809 AC: 435962 AN: 538952 Hom.: 177552 Cov.: 3 AF XY: 0.807 AC XY: 235572 AN XY: 292034

African (AFR) AF: 0.564 AC: 8807 AN: 15618

American (AMR) AF: 0.825 AC: 28347 AN: 34356

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 15735 AN: 19754

East Asian (EAS) AF: 0.805 AC: 25160 AN: 31264

South Asian (SAS) AF: 0.733 AC: 45371 AN: 61874

European-Finnish (FIN) AF: 0.872 AC: 27972 AN: 32086

Middle Eastern (MID) AF: 0.787 AC: 3149 AN: 4002

European-Non Finnish (NFE) AF: 0.830 AC: 257494 AN: 310048

Other (OTH) AF: 0.799 AC: 23927 AN: 29950

GnomAD4 genome AF: 0.755 AC: 114778 AN: 152032 Hom.: 44359 Cov.: 31 AF XY: 0.758 AC XY: 56358 AN XY: 74306

African (AFR) AF: 0.570 AC: 23620 AN: 41432

American (AMR) AF: 0.802 AC: 12242 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2747 AN: 3468

East Asian (EAS) AF: 0.824 AC: 4263 AN: 5174

South Asian (SAS) AF: 0.722 AC: 3481 AN: 4822

European-Finnish (FIN) AF: 0.876 AC: 9251 AN: 10560

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56564 AN: 67992

Other (OTH) AF: 0.786 AC: 1661 AN: 2112

Alfa AF: 0.797 Hom.: 120660

Bravo AF: 0.742

TwinsUK AF: 0.821 AC: 3045

ALSPAC AF: 0.817 AC: 3149

ESP6500AA AF: 0.677 AC: 2061

ESP6500EA AF: 0.870 AC: 5295

ExAC AF: 0.699 AC: 35526

Asia WGS AF: 0.751 AC: 2612 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Platelet-type bleeding disorder 11 Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.95
DANN	Benign	0.087
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00094	N
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.91	T
PhyloP100		-1.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.028
Sift	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.013
MutPred		0.18		Gain of disorder (P = 0.1036)
MPC		0.19
ClinPred		0.00014	T
GERP RS		-0.47
gMVP		0.013
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: rs1671150; hg19: chr19-55525497; COSMIC: COSV107378251; COSMIC: COSV107378251;