1-71047467-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_198719.2(PTGER3):c.111C>G(p.Leu37=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,609,666 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (38 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (36 hom.)
• Consequence: PTGER3 NM_198719.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.897

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]

ZRANB2-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 1-71047467-G-C is Benign according to our data. Variant chr1-71047467-G-C is described in ClinVar as [Benign]. Clinvar id is 777911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.897 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1728/152356) while in subpopulation AFR AF= 0.0388 (1615/41590). AF 95% confidence interval is 0.0373. There are 38 homozygotes in gnomad4. There are 826 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 38 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTGER3	NM_198719.2	c.111C>G	p.Leu37=	synonymous_variant	1/4	ENST00000306666.10
ZRANB2-AS1	NR_038420.1	n.962G>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTGER3	ENST00000306666.10	c.111C>G	p.Leu37=	synonymous_variant	1/4	1	NM_198719.2	A1

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1726 AN: 152238 Hom.: 38 Cov.: 33

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00955

GnomAD3 exomes AF: 0.00279 AC: 658 AN: 235706 Hom.: 16 AF XY: 0.00211 AC XY: 271 AN XY: 128552

Gnomad AFR exome AF: 0.0409

Gnomad AMR exome AF: 0.00160

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000171

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000667

Gnomad OTH exome AF: 0.000523

GnomAD4 exome AF: 0.00117 AC: 1705 AN: 1457310 Hom.: 36 Cov.: 31 AF XY: 0.00100 AC XY: 727 AN XY: 724546

Gnomad4 AFR exome AF: 0.0425

Gnomad4 AMR exome AF: 0.00199

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000822

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000342

Gnomad4 OTH exome AF: 0.00231

GnomAD4 genome AF: 0.0113 AC: 1728 AN: 152356 Hom.: 38 Cov.: 33 AF XY: 0.0111 AC XY: 826 AN XY: 74498

Gnomad4 AFR AF: 0.0388

Gnomad4 AMR AF: 0.00529

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00945

Alfa AF: 0.00335 Hom.: 3

Bravo AF: 0.0130

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	9.7
Dann	Benign	0.84

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: rs5669; hg19: chr1-71513150;