rs41292960

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000959.4(PTGFR):c.23A>T(p.Gln8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,613,658 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0051 ( 51 hom. )

Consequence

PTGFR
NM_000959.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.04

Publications

10 publications found

Variant links:

Genes affected

PTGFR (HGNC:9600): (prostaglandin F receptor) The protein encoded by this gene is member of the G-protein coupled receptor family. This protein is a receptor for prostaglandin F2-alpha (PGF2-alpha), which is known to be a potent luteolytic agent, and may also be involved in modulating intraocular pressure and smooth muscle contraction in uterus. Knockout studies in mice suggest that the interaction of PGF2-alpha with this receptor may initiate parturition in ovarian luteal cells and thus induce luteolysis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PTGFR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003374815).

BP6

Variant 1-78492766-A-T is Benign according to our data. Variant chr1-78492766-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 720742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00406 (619/152364) while in subpopulation SAS AF = 0.0205 (99/4832). AF 95% confidence interval is 0.0172. There are 2 homozygotes in GnomAd4. There are 323 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000959.4. 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
	PTGFR	NM_000959.4	MANE Select	c.23A>T	p.Gln8Leu	missense	Exon 2 of 3	NP_000950.1	P43088-1
	PTGFR	NM_001039585.2		c.23A>T	p.Gln8Leu	missense	Exon 2 of 4	NP_001034674.1	P43088-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTGFR	ENST00000370757.8	TSL:1 MANE Select	c.23A>T	p.Gln8Leu	missense	Exon 2 of 3	ENSP00000359793.3	P43088-1
PTGFR	ENST00000370758.5	TSL:1	c.23A>T	p.Gln8Leu	missense	Exon 3 of 4	ENSP00000359794.1	P43088-1
PTGFR	ENST00000370756.3	TSL:1	c.23A>T	p.Gln8Leu	missense	Exon 2 of 4	ENSP00000359792.3	P43088-2

Frequencies

GnomAD3 genomes

AF:

0.00408

AC:

621

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0209

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00484

Gnomad OTH

AF:

0.00907

GnomAD2 exomes

AF:

0.00560

AC:

1404

AN:

250892

AF XY:

0.00659

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00348

Gnomad ASJ exome

AF:

0.00309

Gnomad EAS exome

AF:

0.000979

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00516

Gnomad OTH exome

AF:

0.00621

GnomAD4 exome

AF:

0.00509

AC:

7438

AN:

1461294

Hom.:

Cov.:

AF XY:

0.00558

AC XY:

4058

AN XY:

726948

show subpopulations

African (AFR)

AF:

0.000538

AC:

AN:

33432

American (AMR)

AF:

0.00416

AC:

186

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00234

AC:

AN:

26086

East Asian (EAS)

AF:

0.00254

AC:

101

AN:

39700

South Asian (SAS)

AF:

0.0191

AC:

1642

AN:

86166

European-Finnish (FIN)

AF:

0.000974

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.0158

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00445

AC:

4944

AN:

1111718

Other (OTH)

AF:

0.00568

AC:

343

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

420

839

1259

1678

2098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

186

372

558

744

930

<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:

0.00406

AC:

619

AN:

152364

Hom.:

Cov.:

AF XY:

0.00434

AC XY:

323

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.000793

AC:

AN:

41592

American (AMR)

AF:

0.00673

AC:

103

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00174

AC:

AN:

5184

South Asian (SAS)

AF:

0.0205

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00484

AC:

329

AN:

68036

Other (OTH)

AF:

0.00898

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

129

161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00373

Hom.:

Bravo

AF:

0.00445

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00582

AC:

707

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.00649

EpiControl

AF:

0.00634

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.0039

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.1

PhyloP100

3.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.3

REVEL

Benign

0.18

Sift

Benign

0.050

Sift4G

Benign

0.16

Polyphen

0.0

Vest4

0.12

MVP

0.42

MPC

0.21

ClinPred

0.016

GERP RS

4.3

Varity_R

0.097

gMVP

0.48

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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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