Genetic Variant ENST00000305392.3:c.-39G>C (chr1-28193722-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000305392.3(PTAFR):c.-39G>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
ENST00000305392.3 splice_region

Scores

Splicing: ADA: 0.003373

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.53

Publications

7 publications found

Variant links:

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]

PTAFR links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000305392.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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: ENST00000305392.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	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

Gene	Transcript	Tags	HGVSc	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.:

show subpopulations

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:

AN:

578

Hom.:

Cov.:

AF XY:

0.0382

AC XY:

AN XY:

340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0351

AC:

AN:

456

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0283

AC:

AN:

106

Other (OTH)

AF:

0.100

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0710

AC:

10795

AN:

152092

Hom.:

606

Cov.:

AF XY:

0.0715

AC XY:

5317

AN XY:

74388

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0401

AC:

2724

AN:

68004

Other (OTH)

AF:

0.0673

AC:

142

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

468

936

1403

1871

2339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0622

Hom.:

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

(source)

DANN

Benign

0.87

PhyloP100

3.5

PromoterAI

-0.34

Neutral

(source)

Mutation Taster

=274/26

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over