dbSNP rs660149: PGR:n.443C>G (chr11-101063583-G-C) – 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.443C>G 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 0.747 in 152,128 control chromosomes in the GnomAD database, including 42,717 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 0.75 ( 42713 hom., cov: 32)

Exomes 𝑓: 0.58 ( 4 hom. )

Consequence

PGR
ENST00000533207.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0810

Publications

15 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:

Genome browser will be placed here

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=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4 link	c.1907-831C>G		intron_variant	Intron 3 of 7	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.1907-831C>G		intron_variant	Intron 3 of 7	1	NM_000926.4	ENSP00000325120.5		P06401-1

Frequencies

GnomAD3 genomes

AF:

0.747

AC:

113572

AN:

151984

Hom.:

42658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.717

Gnomad AMI

AF:

0.620

Gnomad AMR

AF:

0.794

Gnomad ASJ

AF:

0.769

Gnomad EAS

AF:

0.989

Gnomad SAS

AF:

0.766

Gnomad FIN

AF:

0.780

Gnomad MID

AF:

0.697

Gnomad NFE

AF:

0.731

Gnomad OTH

AF:

0.750

GnomAD4 exome

AF:

0.577

AC:

AN:

Hom.:

Cov.:

AF XY:

0.591

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.545

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.747

AC:

113683

AN:

152102

Hom.:

42713

Cov.:

AF XY:

0.751

AC XY:

55837

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.717

AC:

29748

AN:

41490

American (AMR)

AF:

0.794

AC:

12133

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.769

AC:

2668

AN:

3470

East Asian (EAS)

AF:

0.989

AC:

5110

AN:

5166

South Asian (SAS)

AF:

0.767

AC:

3700

AN:

4822

European-Finnish (FIN)

AF:

0.780

AC:

8247

AN:

10576

Middle Eastern (MID)

AF:

0.709

AC:

207

AN:

292

European-Non Finnish (NFE)

AF:

0.731

AC:

49719

AN:

67992

Other (OTH)

AF:

0.752

AC:

1588

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1473

2945

4418

5890

7363

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

856

1712

2568

3424

4280

<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:

0.743

Hom.:

5198

Bravo

AF:

0.747

Asia WGS

AF:

0.894

AC:

3107

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

1.8

(source)

DANN

Benign

0.65

PhyloP100

-0.081

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over