Variant rs500760 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000926.4(PGR):c.2658A>G(p.Gln886Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,604,620 control chromosomes in the GnomAD database, including 49,998 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 0.28 ( 6467 hom., cov: 32)

Exomes 𝑓: 0.24 ( 43531 hom. )

Consequence

PGR
NM_000926.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.518

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP7

Synonymous conserved (PhyloP=-0.518 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGR	NM_000926.4 link	c.2658A>G	p.Gln886Gln	synonymous_variant	8/8	ENST00000325455.10	NP_000917.3	P06401-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10 link	c.2658A>G	p.Gln886Gln	synonymous_variant	8/8	1	NM_000926.4	ENSP00000325120.5		P06401-1

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

42999

AN:

151652

Hom.:

6448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.393

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.386

Gnomad EAS

AF:

0.223

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.293

GnomAD3 exomes

AF:

0.241

AC:

60377

AN:

250118

Hom.:

7908

AF XY:

0.233

AC XY:

31449

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.386

Gnomad AMR exome

AF:

0.266

Gnomad ASJ exome

AF:

0.384

Gnomad EAS exome

AF:

0.223

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.224

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.258

GnomAD4 exome

AF:

0.240

AC:

348580

AN:

1452850

Hom.:

43531

Cov.:

AF XY:

0.236

AC XY:

170514

AN XY:

723172

show subpopulations

Gnomad4 AFR exome

AF:

0.388

Gnomad4 AMR exome

AF:

0.264

Gnomad4 ASJ exome

AF:

0.380

Gnomad4 EAS exome

AF:

0.221

Gnomad4 SAS exome

AF:

0.129

Gnomad4 FIN exome

AF:

0.223

Gnomad4 NFE exome

AF:

0.240

Gnomad4 OTH exome

AF:

0.260

GnomAD4 genome

AF:

0.284

AC:

43080

AN:

151770

Hom.:

6467

Cov.:

AF XY:

0.278

AC XY:

20630

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.394

Gnomad4 AMR

AF:

0.284

Gnomad4 ASJ

AF:

0.386

Gnomad4 EAS

AF:

0.223

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.216

Gnomad4 NFE

AF:

0.238

Gnomad4 OTH

AF:

0.294

Alfa

AF:

0.250

Hom.:

10837

Bravo

AF:

0.296

Asia WGS

AF:

0.193

AC:

673

AN:

3478

EpiCase

AF:

0.249

EpiControl

AF:

0.245

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.88

DANN

Benign

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over