rs5669

Variant names:

• chr1-71047467-G-C
• rs5669
• NM_198719.2:c.111C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_198719.2(PTGER3):​c.111C>G​(p.Leu37Leu) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.897
• Publications: 6 publications found

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:43594): (ZRANB2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 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 VariationId is 777911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198719.2. 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
	PTGER3	NM_198719.2	MANE Select	c.111C>G	p.Leu37Leu	synonymous	Exon 1 of 4	NP_942012.1	P43115-1
	PTGER3	NM_198718.2		c.111C>G	p.Leu37Leu	synonymous	Exon 1 of 4	NP_942011.1	P43115-5
	PTGER3	NM_001126044.2		c.111C>G	p.Leu37Leu	synonymous	Exon 1 of 5	NP_001119516.1	P43115-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTGER3	ENST00000306666.10	TSL:1 MANE Select	c.111C>G	p.Leu37Leu	synonymous	Exon 1 of 4	ENSP00000302313.5	P43115-1
	PTGER3	ENST00000356595.8	TSL:1	c.111C>G	p.Leu37Leu	synonymous	Exon 1 of 4	ENSP00000349003.4	P43115-5
	PTGER3	ENST00000370931.7	TSL:1	c.111C>G	p.Leu37Leu	synonymous	Exon 1 of 5	ENSP00000359969.3	P43115-1

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

GnomAD2 exomes AF: 0.00279 AC: 658 AN: 235706 AF XY: 0.00211

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 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

African (AFR) AF: 0.0425 AC: 1422 AN: 33458

American (AMR) AF: 0.00199 AC: 88 AN: 44290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25842

East Asian (EAS) AF: 0.00 AC: 0 AN: 39510

South Asian (SAS) AF: 0.0000822 AC: 7 AN: 85198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52076

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5766

European-Non Finnish (NFE) AF: 0.0000342 AC: 38 AN: 1110960

Other (OTH) AF: 0.00231 AC: 139 AN: 60210

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

African (AFR) AF: 0.0388 AC: 1615 AN: 41590

American (AMR) AF: 0.00529 AC: 81 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68024

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.00335 Hom.: 3

Bravo AF: 0.0130

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.7
DANN	Benign	0.84
PhyloP100		0.90
PromoterAI		0.017	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs5669; hg19: chr1-71513150;