chr19-55034943-G-C

Variant names:

• chr19-55034943-G-C
• rs1671207
• NM_016363.5:c.35-2405C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016363.5(GP6):​c.35-2405C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,882 control chromosomes in the GnomAD database, including 3,640 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 0.22 (3640 hom., cov: 32)
• Consequence: GP6 NM_016363.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 1 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]

ENSG00000267149 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016363.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	NM_016363.5	MANE Select	c.35-2405C>G		intron	N/A	NP_057447.5	Q9HCN6-1
	GP6	NM_001083899.2		c.35-2405C>G		intron	N/A	NP_001077368.2	Q9HCN6-3
	GP6	NM_001256017.2		c.35-2405C>G		intron	N/A	NP_001242946.2	Q9HCN6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	ENST00000417454.5	TSL:1 MANE Select	c.35-2405C>G		intron	N/A	ENSP00000394922.1	Q9HCN6-1
	GP6	ENST00000310373.7	TSL:1	c.35-2405C>G		intron	N/A	ENSP00000308782.3	Q9HCN6-3
	GP6	ENST00000333884.2	TSL:1	c.35-2405C>G		intron	N/A	ENSP00000334552.2	Q9HCN6-2

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32864 AN: 151762 Hom.: 3631 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.217 AC: 32920 AN: 151882 Hom.: 3640 Cov.: 32 AF XY: 0.217 AC XY: 16088 AN XY: 74210

African (AFR) AF: 0.233 AC: 9671 AN: 41426

American (AMR) AF: 0.212 AC: 3228 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3468

East Asian (EAS) AF: 0.238 AC: 1229 AN: 5154

South Asian (SAS) AF: 0.226 AC: 1090 AN: 4818

European-Finnish (FIN) AF: 0.239 AC: 2521 AN: 10540

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.206 AC: 14018 AN: 67942

Other (OTH) AF: 0.197 AC: 413 AN: 2100

Alfa AF: 0.0803 Hom.: 126

Bravo AF: 0.214

Asia WGS AF: 0.244 AC: 850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.95
DANN	Benign	0.59
PhyloP100		-0.20
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: rs1671207; hg19: chr19-55546311;