19-55015821-G-T

Variant names:

• chr19-55015821-G-T
• rs1671153
• NM_016363.5:c.725-88C>A

Variant summary

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

The NM_001083899.2(GP6):​c.725-88C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 767,388 control chromosomes in the GnomAD database, including 243,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (43186 hom., cov: 31)
  • Exomes 𝑓: 0.80 (200017 hom.)
• Consequence: GP6 NM_001083899.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.03
• Publications: 23 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 (BayesDel_noAF=-0.88).
• BP6: Variant 19-55015821-G-T is Benign according to our data. Variant chr19-55015821-G-T is described in ClinVar as Benign. ClinVar VariationId is 1225054.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: NM_001083899.2. 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.725-88C>A		intron	N/A	NP_057447.5
	GP6	NM_001083899.2		c.725-88C>A		intron	N/A	NP_001077368.2
	GP6	NM_001256017.2		c.671-88C>A		intron	N/A	NP_001242946.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	ENST00000417454.5	TSL:1 MANE Select	c.725-88C>A		intron	N/A	ENSP00000394922.1
	GP6	ENST00000310373.7	TSL:1	c.725-88C>A		intron	N/A	ENSP00000308782.3
	GP6	ENST00000333884.2	TSL:1	c.671-88C>A		intron	N/A	ENSP00000334552.2

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112584 AN: 151834 Hom.: 43182 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.782

GnomAD4 exome AF: 0.803 AC: 494099 AN: 615436 Hom.: 200017 AF XY: 0.801 AC XY: 266643 AN XY: 332716

African (AFR) AF: 0.512 AC: 9301 AN: 18166

American (AMR) AF: 0.820 AC: 30101 AN: 36710

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 16181 AN: 20370

East Asian (EAS) AF: 0.804 AC: 28483 AN: 35422

South Asian (SAS) AF: 0.729 AC: 48273 AN: 66200

European-Finnish (FIN) AF: 0.868 AC: 41140 AN: 47372

Middle Eastern (MID) AF: 0.784 AC: 3255 AN: 4150

European-Non Finnish (NFE) AF: 0.823 AC: 291236 AN: 354054

Other (OTH) AF: 0.792 AC: 26129 AN: 32992

GnomAD4 genome AF: 0.741 AC: 112631 AN: 151952 Hom.: 43186 Cov.: 31 AF XY: 0.745 AC XY: 55316 AN XY: 74274

African (AFR) AF: 0.522 AC: 21567 AN: 41350

American (AMR) AF: 0.798 AC: 12193 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2749 AN: 3472

East Asian (EAS) AF: 0.822 AC: 4243 AN: 5164

South Asian (SAS) AF: 0.721 AC: 3473 AN: 4816

European-Finnish (FIN) AF: 0.876 AC: 9263 AN: 10578

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

European-Non Finnish (NFE) AF: 0.832 AC: 56554 AN: 67992

Other (OTH) AF: 0.780 AC: 1642 AN: 2106

Alfa AF: 0.774 Hom.: 6781

Bravo AF: 0.727

Asia WGS AF: 0.749 AC: 2604 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.40
DANN	Benign	0.81
PhyloP100		-1.0
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: rs1671153; hg19: chr19-55527189; COSMIC: COSV59978023;