Genetic Variant PGR:c.*4791G>A (chr11-101034325-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000926.4(PGR):c.*4791G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 217,570 control chromosomes in the GnomAD database, including 5,987 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 0.16 ( 3061 hom., cov: 33)

Exomes 𝑓: 0.21 ( 2926 hom. )

Consequence

PGR
NM_000926.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.45

Publications

11 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4 link	c.*4791G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10 link	c.*4791G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23946

AN:

152152

Hom.:

3047

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0789

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.690

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.138

GnomAD4 exome

AF:

0.213

AC:

13906

AN:

65300

Hom.:

2926

Cov.:

AF XY:

0.208

AC XY:

6273

AN XY:

30220

show subpopulations

African (AFR)

AF:

0.0837

AC:

247

AN:

2950

American (AMR)

AF:

0.289

AC:

551

AN:

1904

Ashkenazi Jewish (ASJ)

AF:

0.0991

AC:

412

AN:

4156

East Asian (EAS)

AF:

0.700

AC:

6777

AN:

9682

South Asian (SAS)

AF:

0.358

AC:

201

AN:

562

European-Finnish (FIN)

AF:

0.214

AC:

AN:

Middle Eastern (MID)

AF:

0.0747

AC:

AN:

388

European-Non Finnish (NFE)

AF:

0.120

AC:

4792

AN:

40090

Other (OTH)

AF:

0.160

AC:

876

AN:

5470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

394

789

1183

1578

1972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.158

AC:

23984

AN:

152270

Hom.:

3061

Cov.:

AF XY:

0.168

AC XY:

12520

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0789

AC:

3282

AN:

41578

American (AMR)

AF:

0.245

AC:

3741

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

411

AN:

3472

East Asian (EAS)

AF:

0.690

AC:

3562

AN:

5166

South Asian (SAS)

AF:

0.371

AC:

1792

AN:

4832

European-Finnish (FIN)

AF:

0.200

AC:

2117

AN:

10598

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.127

AC:

8616

AN:

68004

Other (OTH)

AF:

0.143

AC:

303

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

969

1938

2907

3876

4845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0894

Hom.:

211

Bravo

AF:

0.158

Asia WGS

AF:

0.514

AC:

1782

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.99

(source)

DANN

Benign

0.62

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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