Genetic Variant PGR:n.926C>A (chr11-101063100-G-T) – 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.926C>A 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 0.194 in 225,018 control chromosomes in the GnomAD database, including 6,255 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 0.19 ( 3855 hom., cov: 32)

Exomes 𝑓: 0.21 ( 2400 hom. )

Consequence

PGR
ENST00000533207.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.79

Publications

7 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=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4 link	c.1907-348C>A		intron_variant	Intron 3 of 7	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10 link	c.1907-348C>A		intron_variant	Intron 3 of 7	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28244

AN:

151966

Hom.:

3849

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.760

Gnomad SAS

AF:

0.428

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.188

GnomAD4 exome

AF:

0.210

AC:

15289

AN:

72934

Hom.:

2400

Cov.:

AF XY:

0.225

AC XY:

8750

AN XY:

38906

show subpopulations

African (AFR)

AF:

0.101

AC:

105

AN:

1042

American (AMR)

AF:

0.298

AC:

1059

AN:

3556

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

266

AN:

1658

East Asian (EAS)

AF:

0.764

AC:

2212

AN:

2896

South Asian (SAS)

AF:

0.361

AC:

3736

AN:

10362

European-Finnish (FIN)

AF:

0.165

AC:

592

AN:

3594

Middle Eastern (MID)

AF:

0.129

AC:

AN:

248

European-Non Finnish (NFE)

AF:

0.145

AC:

6619

AN:

45776

Other (OTH)

AF:

0.176

AC:

668

AN:

3802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

463

926

1390

1853

2316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<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:

0.186

AC:

28264

AN:

152084

Hom.:

3855

Cov.:

AF XY:

0.194

AC XY:

14410

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.119

AC:

4921

AN:

41510

American (AMR)

AF:

0.255

AC:

3893

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

554

AN:

3472

East Asian (EAS)

AF:

0.760

AC:

3912

AN:

5150

South Asian (SAS)

AF:

0.428

AC:

2062

AN:

4814

European-Finnish (FIN)

AF:

0.173

AC:

1832

AN:

10582

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.155

AC:

10546

AN:

67972

Other (OTH)

AF:

0.193

AC:

408

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1023

2046

3069

4092

5115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<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:

0.167

Hom.:

8059

Bravo

AF:

0.188

Asia WGS

AF:

0.581

AC:

2015

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.067

(source)

DANN

Benign

0.55

PhyloP100

-1.8

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