chr1-28193722-C-G

Variant names:

• chr1-28193722-C-G
• rs905907
• ENST00000305392.3:c.-39G>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001164721.2(PTAFR):​c.-121G>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 152,670 control chromosomes in the GnomAD database, including 607 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.071 (606 hom., cov: 31)
  • Exomes 𝑓: 0.035 (1 hom.)
• Consequence: PTAFR NM_001164721.2 splice_region
• Scores: Splicing: ADA: 0.003373
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.53

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTAFR	NM_001164721.2	c.-121G>C		splice_region_variant	Exon 1 of 3		NP_001158193.1
PTAFR	NM_001164722.3	c.-39G>C		splice_region_variant	Exon 1 of 2		NP_001158194.1
PTAFR	NM_001164721.2	c.-121G>C		5_prime_UTR_variant	Exon 1 of 3		NP_001158193.1
PTAFR	NM_001164722.3	c.-39G>C		5_prime_UTR_variant	Exon 1 of 2		NP_001158194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTAFR	ENST00000305392.3	c.-39G>C		splice_region_variant	Exon 1 of 2	1		ENSP00000301974.3
PTAFR	ENST00000305392.3	c.-39G>C		5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000301974.3
PTAFR	ENST00000539896.1	c.-121G>C		splice_region_variant	Exon 1 of 3	2		ENSP00000442658.1
PTAFR	ENST00000539896.1	c.-121G>C		5_prime_UTR_variant	Exon 1 of 3	2		ENSP00000442658.1

Frequencies

GnomAD3 genomes AF: 0.0709 AC: 10774 AN: 151974 Hom.: 606 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0462

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0502

Gnomad FIN AF: 0.0259

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0401

Gnomad OTH AF: 0.0661

GnomAD4 exome AF: 0.0346 AC: 20 AN: 578 Hom.: 1 Cov.: 0 AF XY: 0.0382 AC XY: 13 AN XY: 340

Gnomad4 AFR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0351

Gnomad4 NFE exome AF: 0.0283

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0710 AC: 10795 AN: 152092 Hom.: 606 Cov.: 31 AF XY: 0.0715 AC XY: 5317 AN XY: 74388

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0461

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0515

Gnomad4 FIN AF: 0.0259

Gnomad4 NFE AF: 0.0401

Gnomad4 OTH AF: 0.0673

Alfa AF: 0.0622 Hom.: 59

Bravo AF: 0.0754

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0034
dbscSNV1_RF	Benign	0.012

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

Publications

LitVar

Other links and lift over

dbSNP: rs905907; hg19: chr1-28520233;