chr19-55030031-A-G

Position:

• chr19-55030031-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001083899.2(GP6):​c.325+2108T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,036 control chromosomes in the GnomAD database, including 8,278 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (8278 hom., cov: 32)
• Consequence: GP6 NM_001083899.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GP6	NM_001083899.2	c.325+2108T>C		intron_variant		ENST00000310373.7	NP_001077368.2
GP6-AS1	XR_001754012.3	n.122-12769A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7	c.325+2108T>C		intron_variant		1	NM_001083899.2	ENSP00000308782
GP6-AS1	ENST00000593060.5	n.156-12769A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49320 AN: 151918 Hom.: 8271 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.333

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.325 AC: 49356 AN: 152036 Hom.: 8278 Cov.: 32 AF XY: 0.328 AC XY: 24353 AN XY: 74322

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.334

Alfa AF: 0.299 Hom.: 10543

Bravo AF: 0.329

Asia WGS AF: 0.409 AC: 1422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.1
DANN	Benign	0.77

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: rs12610286; hg19: chr19-55541399;