dbSNP rs1654431: ENSG00000267149:n.1001+6515C>T (chr19-55038390-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000585492.1(ENSG00000267149):n.1001+6515C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 660,540 control chromosomes in the GnomAD database, including 81,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17100 hom., cov: 30)

Exomes 𝑓: 0.50 ( 63990 hom. )

Consequence

ENSG00000267149
ENST00000585492.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.58

Variant links:

Genes affected

ENSG00000267149 (HGNC:):

ENSG00000267149 links:

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

GP6-AS1 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 19-55038390-G-A is Benign according to our data. Variant chr19-55038390-G-A is described in ClinVar as [Benign]. Clinvar id is 1278923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP6	NM_001083899.2 link	c.-154C>T		upstream_gene_variant		ENST00000310373.7	NP_001077368.2	Q9HCN6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7 link	c.-154C>T		upstream_gene_variant		1	NM_001083899.2	ENSP00000308782.3		Q9HCN6-3
GP6	ENST00000417454.5 link	c.-154C>T		upstream_gene_variant		1		ENSP00000394922.1		Q9HCN6-1

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71135

AN:

151708

Hom.:

17098

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.522

Gnomad AMR

AF:

0.418

Gnomad ASJ

AF:

0.413

Gnomad EAS

AF:

0.584

Gnomad SAS

AF:

0.415

Gnomad FIN

AF:

0.552

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.482

GnomAD4 exome

AF:

0.497

AC:

252736

AN:

508714

Hom.:

63990

AF XY:

0.494

AC XY:

134215

AN XY:

271682

show subpopulations

Gnomad4 AFR exome

AF:

0.377

Gnomad4 AMR exome

AF:

0.422

Gnomad4 ASJ exome

AF:

0.410

Gnomad4 EAS exome

AF:

0.577

Gnomad4 SAS exome

AF:

0.427

Gnomad4 FIN exome

AF:

0.550

Gnomad4 NFE exome

AF:

0.514

Gnomad4 OTH exome

AF:

0.488

GnomAD4 genome

AF:

0.469

AC:

71163

AN:

151826

Hom.:

17100

Cov.:

AF XY:

0.471

AC XY:

34949

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.382

Gnomad4 AMR

AF:

0.417

Gnomad4 ASJ

AF:

0.413

Gnomad4 EAS

AF:

0.585

Gnomad4 SAS

AF:

0.415

Gnomad4 FIN

AF:

0.552

Gnomad4 NFE

AF:

0.517

Gnomad4 OTH

AF:

0.482

Alfa

AF:

0.500

Hom.:

28813

Bravo

AF:

0.455

Asia WGS

AF:

0.459

AC:

1597

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.27

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over