ENST00000310373.7:c.1727G>A

Variant names:

• chr19-55014218-C-T
• rs10418074
• ENST00000310373.7:c.1727G>A

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.1727G>A​(p.Arg576Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 793,436 control chromosomes in the GnomAD database, including 1,362 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (387 hom., cov: 32)
  • Exomes 𝑓: 0.052 (975 hom.)
• Consequence: GP6 ENST00000310373.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.266
• Publications: 4 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=0.0018121004).
• BP6: Variant 19-55014218-C-T is Benign according to our data. Variant chr19-55014218-C-T is described in ClinVar as Benign. ClinVar VariationId is 257414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 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.*703G>A		3_prime_UTR	Exon 8 of 8	NP_057447.5
	GP6	NM_001083899.2		c.1727G>A	p.Arg576Lys	missense	Exon 8 of 8	NP_001077368.2
	GP6	NM_001256017.2		c.*703G>A		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.1727G>A	p.Arg576Lys	missense	Exon 8 of 8	ENSP00000308782.3
	GP6	ENST00000417454.5	TSL:1 MANE Select	c.*703G>A		3_prime_UTR	Exon 8 of 8	ENSP00000394922.1
	GP6	ENST00000333884.2	TSL:1	c.*703G>A		3_prime_UTR	Exon 7 of 7	ENSP00000334552.2

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9878 AN: 152074 Hom.: 388 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0438

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.0556

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.0562

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0498

Gnomad OTH AF: 0.0565

GnomAD2 exomes AF: 0.0519 AC: 9410 AN: 181162 AF XY: 0.0530

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.0250

Gnomad ASJ exome AF: 0.0396

Gnomad EAS exome AF: 0.0544

Gnomad FIN exome AF: 0.0622

Gnomad NFE exome AF: 0.0507

Gnomad OTH exome AF: 0.0478

GnomAD4 exome AF: 0.0518 AC: 33223 AN: 641244 Hom.: 975 Cov.: 8 AF XY: 0.0524 AC XY: 18133 AN XY: 345768

African (AFR) AF: 0.105 AC: 1931 AN: 18346

American (AMR) AF: 0.0277 AC: 1046 AN: 37816

Ashkenazi Jewish (ASJ) AF: 0.0406 AC: 838 AN: 20658

East Asian (EAS) AF: 0.0447 AC: 1570 AN: 35140

South Asian (SAS) AF: 0.0624 AC: 4171 AN: 66846

European-Finnish (FIN) AF: 0.0637 AC: 2367 AN: 37138

Middle Eastern (MID) AF: 0.0292 AC: 119 AN: 4078

European-Non Finnish (NFE) AF: 0.0502 AC: 19434 AN: 387426

Other (OTH) AF: 0.0517 AC: 1747 AN: 33796

GnomAD4 genome AF: 0.0649 AC: 9879 AN: 152192 Hom.: 387 Cov.: 32 AF XY: 0.0642 AC XY: 4779 AN XY: 74400

African (AFR) AF: 0.104 AC: 4336 AN: 41512

American (AMR) AF: 0.0438 AC: 669 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3470

East Asian (EAS) AF: 0.0556 AC: 288 AN: 5182

South Asian (SAS) AF: 0.0647 AC: 312 AN: 4820

European-Finnish (FIN) AF: 0.0562 AC: 596 AN: 10610

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0498 AC: 3384 AN: 68000

Other (OTH) AF: 0.0550 AC: 116 AN: 2110

Alfa AF: 0.0325 Hom.: 32

Bravo AF: 0.0669

TwinsUK AF: 0.0445 AC: 165

ALSPAC AF: 0.0485 AC: 187

ESP6500AA AF: 0.0810 AC: 310

ESP6500EA AF: 0.0444 AC: 359

ExAC AF: 0.0508 AC: 6028

Asia WGS AF: 0.0590 AC: 205 AN: 3478

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
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	10
DANN	Benign	0.87
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.014	N
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.27
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.030
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.076	T
Polyphen		0.22	B
Vest4		0.053
MPC		0.22
ClinPred		0.013	T
GERP RS		0.23
gMVP		0.034
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: rs10418074; hg19: chr19-55525586; COSMIC: COSV59977213; COSMIC: COSV59977213;