Genetic Variant PGR:n.2207T>C (chr11-101039078-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000533207.5(PGR):n.2207T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,551,512 control chromosomes in the GnomAD database, including 47,866 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 ( 6474 hom., cov: 32)

Exomes 𝑓: 0.24 ( 41392 hom. )

Consequence

PGR
ENST00000533207.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

Publications

23 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=-0.63).

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 rank	MANE	Protein	UniProt
PGR	NM_000926.4 link	c.*38T>C		3_prime_UTR_variant	Exon 8 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.*38T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_000926.4	ENSP00000325120.5		P06401-1

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

42987

AN:

151562

Hom.:

6455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.393

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.386

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.293

GnomAD2 exomes

AF:

0.241

AC:

59220

AN:

246110

AF XY:

0.232

show subpopulations

Gnomad AFR exome

AF:

0.385

Gnomad AMR exome

AF:

0.266

Gnomad ASJ exome

AF:

0.383

Gnomad EAS exome

AF:

0.223

Gnomad FIN exome

AF:

0.225

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.258

GnomAD4 exome

AF:

0.238

AC:

333808

AN:

1399832

Hom.:

41392

Cov.:

AF XY:

0.234

AC XY:

163977

AN XY:

699824

show subpopulations

African (AFR)

AF:

0.386

AC:

12425

AN:

32152

American (AMR)

AF:

0.263

AC:

11658

AN:

44270

Ashkenazi Jewish (ASJ)

AF:

0.379

AC:

9701

AN:

25572

East Asian (EAS)

AF:

0.221

AC:

8654

AN:

39206

South Asian (SAS)

AF:

0.129

AC:

10967

AN:

84946

European-Finnish (FIN)

AF:

0.223

AC:

11708

AN:

52496

Middle Eastern (MID)

AF:

0.236

AC:

1329

AN:

5640

European-Non Finnish (NFE)

AF:

0.239

AC:

252303

AN:

1057320

Other (OTH)

AF:

0.259

AC:

15063

AN:

58230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

11615

23230

34845

46460

58075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8516

17032

25548

34064

42580

<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:

0.284

AC:

43068

AN:

151680

Hom.:

6474

Cov.:

AF XY:

0.278

AC XY:

20616

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.394

AC:

16306

AN:

41386

American (AMR)

AF:

0.284

AC:

4320

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.386

AC:

1338

AN:

3462

East Asian (EAS)

AF:

0.222

AC:

1146

AN:

5162

South Asian (SAS)

AF:

0.128

AC:

616

AN:

4828

European-Finnish (FIN)

AF:

0.217

AC:

2296

AN:

10582

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.238

AC:

16113

AN:

67736

Other (OTH)

AF:

0.294

AC:

620

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1550

3099

4649

6198

7748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.266

Hom.:

6934

Bravo

AF:

0.296

Asia WGS

AF:

0.192

AC:

668

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.4

(source)

DANN

Benign

0.68

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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