rs2481974

Positions:

• chr1-28190868-C-A

Variant summary

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

The ENST00000305392.3(PTAFR):​c.-39+2854G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,958 control chromosomes in the GnomAD database, including 14,528 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 0.41 (14528 hom., cov: 31)
• Consequence: PTAFR ENST00000305392.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665

Genes affected

PTAFR (HGNC:9582): (platelet activating factor receptor) This gene encodes a seven-transmembrane G-protein-coupled receptor for platelet-activating factor (PAF) that localizes to lipid rafts and/or caveolae in the cell membrane. PAF (1-0-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) is a phospholipid that plays a significant role in oncogenic transformation, tumor growth, angiogenesis, metastasis, and pro-inflammatory processes. Binding of PAF to the PAF-receptor (PAFR) stimulates numerous signal transduction pathways including phospholipase C, D, A2, mitogen-activated protein kinases (MAPKs), and the phosphatidylinositol-calcium second messenger system. Following PAFR activation, cells become rapidly desensitized and this refractory state is dependent on PAFR phosphorylation, internalization, and down-regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTAFR	NM_001164721.2	c.-121+2854G>T		intron_variant			NP_001158193.1
PTAFR	NM_001164722.3	c.-39+2854G>T		intron_variant			NP_001158194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTAFR	ENST00000305392.3	c.-39+2854G>T		intron_variant		1		ENSP00000301974	P1
PTAFR	ENST00000539896.1	c.-121+2854G>T		intron_variant		2		ENSP00000442658	P1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62864 AN: 151840 Hom.: 14493 Cov.: 31

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.0993

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.414 AC: 62955 AN: 151958 Hom.: 14528 Cov.: 31 AF XY: 0.407 AC XY: 30247 AN XY: 74286

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.0993

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.402

Alfa AF: 0.393 Hom.: 1512

Bravo AF: 0.423

Asia WGS AF: 0.229 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.69
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2481974; hg19: chr1-28517379;