Variant chr1-78492766-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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 criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.04

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 made for transcript

Verdict is Benign. Variant got -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]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGFR	NM_000959.4 link	c.23A>T	p.Gln8Leu	missense_variant	2/3	ENST00000370757.8	NP_000950.1	P43088-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PTGFR	ENST00000370757.8 link	c.23A>T	p.Gln8Leu	missense_variant	2/3	1	NM_000959.4	ENSP00000359793.3	P43088-1
PTGFR	ENST00000370758.5 link	c.23A>T	p.Gln8Leu	missense_variant	3/4	1		ENSP00000359794.1	P43088-1
PTGFR	ENST00000370756.3 link	c.23A>T	p.Gln8Leu	missense_variant	2/4	1		ENSP00000359792.3	P43088-2
PTGFR	ENST00000497923.5 link	n.23A>T		non_coding_transcript_exon_variant	2/5	3		ENSP00000432599.1	F2Z2Z6

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

GnomAD3 exomes

AF:

0.00560

AC:

1404

AN:

250892

Hom.:

AF XY:

0.00659

AC XY:

894

AN XY:

135598

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 SAS exome

AF:

0.0190

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

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.00416

Gnomad4 ASJ exome

AF:

0.00234

Gnomad4 EAS exome

AF:

0.00254

Gnomad4 SAS exome

AF:

0.0191

Gnomad4 FIN exome

AF:

0.000974

Gnomad4 NFE exome

AF:

0.00445

Gnomad4 OTH exome

AF:

0.00568

GnomAD4 genome

AF:

0.00406

AC:

619

AN:

152364

Hom.:

Cov.:

AF XY:

0.00434

AC XY:

323

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000793

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0205

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00484

Gnomad4 OTH

AF:

0.00898

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.0039

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.66

.;T;T

MetaRNN

Benign

0.0034

T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.1

L;L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.050

D;D;T

Sift4G

Benign

0.16

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.12

MVP

0.42

MPC

0.21

ClinPred

0.016

GERP RS

4.3

Varity_R

0.097

gMVP

0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over