chr1-78492766-A-T

Position:

• chr1-78492766-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000370757.8(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 ENST00000370757.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.04

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]

ACMG classification

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	c.23A>T	p.Gln8Leu	missense_variant	2/3	ENST00000370757.8	NP_000950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGFR	ENST00000370757.8	c.23A>T	p.Gln8Leu	missense_variant	2/3	1	NM_000959.4	ENSP00000359793	P1
PTGFR	ENST00000370758.5	c.23A>T	p.Gln8Leu	missense_variant	3/4	1		ENSP00000359794	P1
PTGFR	ENST00000370756.3	c.23A>T	p.Gln8Leu	missense_variant	2/4	1		ENSP00000359792
PTGFR	ENST00000497923.5	c.23A>T	p.Gln8Leu	missense_variant, NMD_transcript_variant	2/5	3		ENSP00000432599

Frequencies

GnomAD3 genomes AF: 0.00408 AC: 621 AN: 152246 Hom.: 3 Cov.: 33

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.: 10 AF XY: 0.00659 AC XY: 894 AN XY: 135598

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.: 51 Cov.: 30 AF XY: 0.00558 AC XY: 4058 AN XY: 726948

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.: 2 Cov.: 33 AF XY: 0.00434 AC XY: 323 AN XY: 74500

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.: 1

Bravo AF: 0.00445

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00701 AC: 27

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00570 AC: 49

ExAC AF: 0.00582 AC: 707

Asia WGS AF: 0.0170 AC: 58 AN: 3478

EpiCase AF: 0.00649

EpiControl AF: 0.00634

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.0039
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.66	.;T;T
MetaRNN	Benign	0.0034	T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.1	L;L;L
MutationTaster	Benign	0.62	N;N;N
PrimateAI	Benign	0.33	T
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	T
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

Other links and lift over

dbSNP: rs41292960; hg19: chr1-78958451; COSMIC: COSV99056347;