dbSNP rs572698: PGR:c.2646+115G>T (chr11-101041830-C-A) – 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.2646+115G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 906,620 control chromosomes in the GnomAD database, including 29,238 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 ( 6424 hom., cov: 32)

Exomes 𝑓: 0.24 ( 22814 hom. )

Consequence

PGR
NM_000926.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.132

Publications

4 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4 link	c.2646+115G>T		intron_variant	Intron 7 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.2646+115G>T		intron_variant	Intron 7 of 7	1	NM_000926.4	ENSP00000325120.5		P06401-1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42868

AN:

151282

Hom.:

6407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.392

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.223

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.260

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.291

GnomAD4 exome

AF:

0.240

AC:

181330

AN:

755228

Hom.:

22814

Cov.:

AF XY:

0.234

AC XY:

92057

AN XY:

393456

show subpopulations

African (AFR)

AF:

0.385

AC:

7107

AN:

18452

American (AMR)

AF:

0.257

AC:

8447

AN:

32848

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

7669

AN:

20170

East Asian (EAS)

AF:

0.221

AC:

7216

AN:

32622

South Asian (SAS)

AF:

0.129

AC:

8082

AN:

62886

European-Finnish (FIN)

AF:

0.221

AC:

8437

AN:

38196

Middle Eastern (MID)

AF:

0.237

AC:

662

AN:

2792

European-Non Finnish (NFE)

AF:

0.243

AC:

124072

AN:

510822

Other (OTH)

AF:

0.264

AC:

9638

AN:

36440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

6922

13845

20767

27690

34612

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2810

5620

8430

11240

14050

<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:

42947

AN:

151392

Hom.:

6424

Cov.:

AF XY:

0.278

AC XY:

20549

AN XY:

73924

show subpopulations

African (AFR)

AF:

0.392

AC:

16207

AN:

41304

American (AMR)

AF:

0.284

AC:

4317

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

1341

AN:

3468

East Asian (EAS)

AF:

0.223

AC:

1143

AN:

5128

South Asian (SAS)

AF:

0.128

AC:

611

AN:

4788

European-Finnish (FIN)

AF:

0.217

AC:

2254

AN:

10372

Middle Eastern (MID)

AF:

0.266

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.238

AC:

16147

AN:

67824

Other (OTH)

AF:

0.292

AC:

614

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1521

3042

4563

6084

7605

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:

0.270

Hom.:

784

Bravo

AF:

0.296

Asia WGS

AF:

0.193

AC:

671

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.14

PhyloP100

0.13

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