3-194398451-C-T

Variant names:

• chr3-194398451-C-T
• rs2185479
• NM_004488.2:c.-2-167G>A

Variant summary

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

The NM_004488.2(GP5):​c.-2-167G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00629 in 650,900 control chromosomes in the GnomAD database, including 126 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 0.019 (96 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (30 hom.)
• Consequence: GP5 NM_004488.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328

Genes affected

GP5 (HGNC:4443): (glycoprotein V platelet) Human platelet glycoprotein V (GP5) is a part of the Ib-V-IX system of surface glycoproteins that constitute the receptor for von Willebrand factor (VWF; MIM 613160) and mediate the adhesion of platelets to injured vascular surfaces in the arterial circulation, a critical initiating event in hemostasis. The main portion of the receptor is a heterodimer composed of 2 polypeptide chains, an alpha chain (GP1BA; MIM 606672) and a beta chain (GP1BB; MIM 138720), that are linked by disulfide bonds. The complete receptor complex includes noncovalent association of the alpha and beta subunits with platelet glycoprotein IX (GP9; MIM 173515) and GP5. Mutations in GP1BA, GP1BB, and GP9 have been shown to cause Bernard-Soulier syndrome (MIM 231200), a bleeding disorder (review by Lopez et al., 1998 [PubMed 9616133]).[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP5	NM_004488.2	c.-2-167G>A		intron_variant	Intron 1 of 1	ENST00000692618.1	NP_004479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP5	ENST00000692618.1	c.-2-167G>A		intron_variant	Intron 1 of 1		NM_004488.2	ENSP00000509337.1
GP5	ENST00000401815.1	c.-169G>A		upstream_gene_variant		6		ENSP00000383931.1

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2949 AN: 152254 Hom.: 96 Cov.: 33

Gnomad AFR AF: 0.0673

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.00229 AC: 1142 AN: 498528 Hom.: 30 AF XY: 0.00192 AC XY: 492 AN XY: 256892

Gnomad4 AFR exome AF: 0.0653

Gnomad4 AMR exome AF: 0.00485

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000162

Gnomad4 SAS exome AF: 0.000315

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000744

Gnomad4 OTH exome AF: 0.00578

GnomAD4 genome AF: 0.0194 AC: 2954 AN: 152372 Hom.: 96 Cov.: 33 AF XY: 0.0190 AC XY: 1414 AN XY: 74518

Gnomad4 AFR AF: 0.0672

Gnomad4 AMR AF: 0.00784

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00509 Hom.: 7

Bravo AF: 0.0223

Asia WGS AF: 0.00318 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.2
DANN	Benign	0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2185479; hg19: chr3-194119180;