rs1654431

Variant names:

• chr19-55038390-G-A
• rs1654431
• ENST00000585492.1:n.1001+6515C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-55038390-G-A
• chr19-55038390-G-C
• chr19-55038390-G-T

Variant summary

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

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.58
• Publications: 22 publications found

Genes affected

ENSG00000267149 (HGNC:):

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

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 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 11

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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_016363.5	c.-154C>T		upstream_gene_variant		ENST00000417454.5	NP_057447.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000417454.5	c.-154C>T		upstream_gene_variant		1	NM_016363.5	ENSP00000394922.1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71135 AN: 151708 Hom.: 17098 Cov.: 30

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

African (AFR) AF: 0.377 AC: 5347 AN: 14196

American (AMR) AF: 0.422 AC: 11509 AN: 27298

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 6748 AN: 16470

East Asian (EAS) AF: 0.577 AC: 18227 AN: 31600

South Asian (SAS) AF: 0.427 AC: 23513 AN: 55024

European-Finnish (FIN) AF: 0.550 AC: 18314 AN: 33286

Middle Eastern (MID) AF: 0.456 AC: 1024 AN: 2248

European-Non Finnish (NFE) AF: 0.514 AC: 154178 AN: 300174

Other (OTH) AF: 0.488 AC: 13876 AN: 28418

GnomAD4 genome AF: 0.469 AC: 71163 AN: 151826 Hom.: 17100 Cov.: 30 AF XY: 0.471 AC XY: 34949 AN XY: 74194

African (AFR) AF: 0.382 AC: 15804 AN: 41380

American (AMR) AF: 0.417 AC: 6364 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1432 AN: 3470

East Asian (EAS) AF: 0.585 AC: 3005 AN: 5140

South Asian (SAS) AF: 0.415 AC: 1998 AN: 4814

European-Finnish (FIN) AF: 0.552 AC: 5815 AN: 10532

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35111 AN: 67924

Other (OTH) AF: 0.482 AC: 1018 AN: 2110

Alfa AF: 0.495 Hom.: 70603

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

Submissions by phenotype

not provided Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.27
DANN	Benign	0.80
PhyloP100		-2.6
PromoterAI		0.044	Neutral
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

Other links and lift over

dbSNP: rs1654431; hg19: chr19-55549758;