19-55014156-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001083899.2(GP6):c.1789A>C(p.Thr597Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 700,030 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (57 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (33 hom.)
• Consequence: GP6 NM_001083899.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.748

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032471418).
• BP6: Variant 19-55014156-T-G is Benign according to our data. Variant chr19-55014156-T-G is described in ClinVar as [Benign]. Clinvar id is 2126723.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2037/152140) while in subpopulation AFR AF= 0.046 (1910/41482). AF 95% confidence interval is 0.0443. There are 57 homozygotes in gnomad4. There are 926 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GP6	NM_001083899.2	c.1789A>C	p.Thr597Pro	missense_variant	8/8	ENST00000310373.7
GP6-AS1	XR_001754012.3	n.121+7692T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GP6	ENST00000310373.7	c.1789A>C	p.Thr597Pro	missense_variant	8/8	1	NM_001083899.2
GP6-AS1	ENST00000593060.5	n.155+7692T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2037 AN: 152022 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00911

GnomAD3 exomes AF: 0.00286 AC: 380 AN: 132898 Hom.: 16 AF XY: 0.00233 AC XY: 168 AN XY: 72186

Gnomad AFR exome AF: 0.0478

Gnomad AMR exome AF: 0.00208

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000880

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000396

Gnomad OTH exome AF: 0.00195

GnomAD4 exome AF: 0.00183 AC: 1004 AN: 547890 Hom.: 33 Cov.: 4 AF XY: 0.00140 AC XY: 417 AN XY: 296818

Gnomad4 AFR exome AF: 0.0480

Gnomad4 AMR exome AF: 0.00297

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000966

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000571

Gnomad4 OTH exome AF: 0.00368

GnomAD4 genome AF: 0.0134 AC: 2037 AN: 152140 Hom.: 57 Cov.: 32 AF XY: 0.0124 AC XY: 926 AN XY: 74388

Gnomad4 AFR AF: 0.0460

Gnomad4 AMR AF: 0.00654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00901

Alfa AF: 0.00214 Hom.: 6

Bravo AF: 0.0157

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0253 AC: 91

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00184 AC: 182

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	13
Dann	Benign	0.60
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.011	N
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.063
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.89	P
Vest4		0.20
MVP		0.085
MPC		0.57
ClinPred		0.072	T
GERP RS		-0.47
gMVP		0.11

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

Publications

LitVar

Other links and lift over

dbSNP: rs115459014; hg19: chr19-55525524;