rs905907

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164721.2. 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
	PTAFR	NM_001164721.2		c.-121G>C		splice_region	Exon 1 of 3	NP_001158193.1	P25105
	PTAFR	NM_001164722.3		c.-39G>C		splice_region	Exon 1 of 2	NP_001158194.1	P25105
	PTAFR	NM_001164721.2		c.-121G>C		5_prime_UTR	Exon 1 of 3	NP_001158193.1	P25105

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTAFR	ENST00000305392.3	TSL:1	c.-39G>C		splice_region	Exon 1 of 2	ENSP00000301974.3	P25105
	PTAFR	ENST00000305392.3	TSL:1	c.-39G>C		5_prime_UTR	Exon 1 of 2	ENSP00000301974.3	P25105
	PTAFR	ENST00000539896.1	TSL:2	c.-121G>C		splice_region	Exon 1 of 3	ENSP00000442658.1	P25105

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.0351 AC: 16 AN: 456

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0283 AC: 3 AN: 106

Other (OTH) AF: 0.100 AC: 1 AN: 10

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

African (AFR) AF: 0.150 AC: 6234 AN: 41454

American (AMR) AF: 0.0461 AC: 703 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 327 AN: 3470

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5170

South Asian (SAS) AF: 0.0515 AC: 248 AN: 4818

European-Finnish (FIN) AF: 0.0259 AC: 275 AN: 10600

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0401 AC: 2724 AN: 68004

Other (OTH) AF: 0.0673 AC: 142 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.87
PhyloP100		3.5
PromoterAI		-0.34	Neutral
Mutation Taster		=274/26	polymorphism (auto)

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

Other links and lift over

dbSNP: rs905907; hg19: chr1-28520233;