dbSNP rs1379130: PGR:p.Gly393Gly (chr11-101127892-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000926.4(PGR):c.1179C>T(p.Gly393Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,599,908 control chromosomes in the GnomAD database, including 80,947 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5660 hom., cov: 32)

Exomes 𝑓: 0.31 ( 75287 hom. )

Consequence

PGR
NM_000926.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00300

Publications

17 publications found

Variant links:

Genes affected

PGR (HGNC:8910): (progesterone receptor) This gene encodes a member of the steroid receptor superfamily. The encoded protein mediates the physiological effects of progesterone, which plays a central role in reproductive events associated with the establishment and maintenance of pregnancy. This gene uses two distinct promotors and translation start sites in the first exon to produce several transcript variants, both protein coding and non-protein coding. Two of the isoforms (A and B) are identical except for an additional 165 amino acids found in the N-terminus of isoform B and mediate their own response genes and physiologic effects with little overlap. [provided by RefSeq, Sep 2015]

PGR links:

PGR-AS1 (HGNC:52650): (PGR antisense RNA 1)

PGR-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP7

Synonymous conserved (PhyloP=-0.003 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4 link	c.1179C>T	p.Gly393Gly	synonymous_variant	Exon 1 of 8	ENST00000325455.10	NP_000917.3	P06401-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10 link	c.1179C>T	p.Gly393Gly	synonymous_variant	Exon 1 of 8	1	NM_000926.4	ENSP00000325120.5		P06401-1

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37007

AN:

150556

Hom.:

5661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0778

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.00615

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.250

GnomAD2 exomes

AF:

0.268

AC:

61341

AN:

229144

AF XY:

0.273

show subpopulations

Gnomad AFR exome

AF:

0.0757

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.225

Gnomad EAS exome

AF:

0.00541

Gnomad FIN exome

AF:

0.388

Gnomad NFE exome

AF:

0.348

Gnomad OTH exome

AF:

0.297

GnomAD4 exome

AF:

0.313

AC:

453563

AN:

1449230

Hom.:

75287

Cov.:

AF XY:

0.311

AC XY:

224497

AN XY:

721396

show subpopulations

African (AFR)

AF:

0.0702

AC:

2319

AN:

33020

American (AMR)

AF:

0.236

AC:

10389

AN:

44030

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

5808

AN:

25690

East Asian (EAS)

AF:

0.00236

AC:

AN:

39042

South Asian (SAS)

AF:

0.216

AC:

18635

AN:

86098

European-Finnish (FIN)

AF:

0.382

AC:

18436

AN:

48298

Middle Eastern (MID)

AF:

0.308

AC:

1768

AN:

5740

European-Non Finnish (NFE)

AF:

0.343

AC:

379602

AN:

1107656

Other (OTH)

AF:

0.277

AC:

16514

AN:

59656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

19365

38729

58094

77458

96823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.246

AC:

37003

AN:

150678

Hom.:

5660

Cov.:

AF XY:

0.248

AC XY:

18228

AN XY:

73634

show subpopulations

African (AFR)

AF:

0.0777

AC:

3189

AN:

41048

American (AMR)

AF:

0.248

AC:

3765

AN:

15200

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

742

AN:

3458

East Asian (EAS)

AF:

0.00617

AC:

AN:

4864

South Asian (SAS)

AF:

0.199

AC:

940

AN:

4716

European-Finnish (FIN)

AF:

0.385

AC:

4042

AN:

10496

Middle Eastern (MID)

AF:

0.303

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.347

AC:

23441

AN:

67616

Other (OTH)

AF:

0.246

AC:

514

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

1354

2709

4063

5418

6772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.289

Hom.:

2908

Bravo

AF:

0.226

Asia WGS

AF:

0.104

AC:

363

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

-0.0030

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1379130

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over