1-70952978-TG-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000356595.8(PTGER3):c.1185del(p.Asn395LysfsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00782 in 1,613,250 control chromosomes in the GnomAD database, including 68 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0080 (64 hom.)
• Consequence: PTGER3 ENST00000356595.8 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.531

Genes affected

PTGER3 (HGNC:9595): (prostaglandin E receptor 3) The protein encoded by this gene is a member of the G-protein coupled receptor family. This protein is one of four receptors identified for prostaglandin E2 (PGE2). This receptor may have many biological functions, which involve digestion, nervous system, kidney reabsorption, and uterine contraction activities. Studies of the mouse counterpart suggest that this receptor may also mediate adrenocorticotropic hormone response as well as fever generation in response to exogenous and endogenous stimuli. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-70952978-TG-T is Benign according to our data. Variant chr1-70952978-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 770488.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGER3	NM_198718.2	c.1185del	p.Asn395LysfsTer9	frameshift_variant	4/4
PTGER3	NM_001126044.2	c.*104del		3_prime_UTR_variant	5/5
PTGER3	NM_198714.2	c.*23+784del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGER3	ENST00000356595.8	c.1185del	p.Asn395LysfsTer9	frameshift_variant	4/4	1
PTGER3	ENST00000370931.7	c.*23+784del		intron_variant		1		A1
PTGER3	ENST00000460330.5	c.1104+784del		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.00569 AC: 865 AN: 152146 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00518

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00866

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00901

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00541 AC: 1351 AN: 249840 Hom.: 7 AF XY: 0.00546 AC XY: 738 AN XY: 135190

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00310

Gnomad ASJ exome AF: 0.00328

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000817

Gnomad FIN exome AF: 0.00911

Gnomad NFE exome AF: 0.00834

Gnomad OTH exome AF: 0.00556

GnomAD4 exome AF: 0.00804 AC: 11749 AN: 1460986 Hom.: 64 Cov.: 31 AF XY: 0.00786 AC XY: 5714 AN XY: 726816

Gnomad4 AFR exome AF: 0.00114

Gnomad4 AMR exome AF: 0.00309

Gnomad4 ASJ exome AF: 0.00356

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00106

Gnomad4 FIN exome AF: 0.00847

Gnomad4 NFE exome AF: 0.00947

Gnomad4 OTH exome AF: 0.00640

GnomAD4 genome AF: 0.00568 AC: 865 AN: 152264 Hom.: 4 Cov.: 32 AF XY: 0.00545 AC XY: 406 AN XY: 74462

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.00517

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00866

Gnomad4 NFE AF: 0.00901

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00647 Hom.: 0

Bravo AF: 0.00527

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00942

EpiControl AF: 0.00884

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 30, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs568967213; hg19: chr1-71418661; COSMIC: COSV63037073; COSMIC: COSV63037073;