Genetic Variant PGR:c.*4138A>C (chr11-101034978-T-G) – 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.*4138A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 193,660 control chromosomes in the GnomAD database, including 7,971 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 0.29 ( 6454 hom., cov: 33)

Exomes 𝑓: 0.27 ( 1517 hom. )

Consequence

PGR
NM_000926.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0440

Publications

6 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 (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4 link	c.*4138A>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.*4138A>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_000926.4	ENSP00000325120.5		P06401-1

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43317

AN:

151952

Hom.:

6436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.370

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.218

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.306

GnomAD4 exome

AF:

0.270

AC:

11238

AN:

41590

Hom.:

1517

Cov.:

AF XY:

0.271

AC XY:

5205

AN XY:

19206

show subpopulations

African (AFR)

AF:

0.357

AC:

614

AN:

1720

American (AMR)

AF:

0.307

AC:

333

AN:

1084

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1011

AN:

2648

East Asian (EAS)

AF:

0.234

AC:

1662

AN:

7090

South Asian (SAS)

AF:

0.146

AC:

AN:

356

European-Finnish (FIN)

AF:

0.0909

AC:

AN:

Middle Eastern (MID)

AF:

0.262

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.261

AC:

6515

AN:

25006

Other (OTH)

AF:

0.288

AC:

981

AN:

3404

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

416

832

1247

1663

2079

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.285

AC:

43392

AN:

152070

Hom.:

6454

Cov.:

AF XY:

0.279

AC XY:

20758

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.370

AC:

15347

AN:

41454

American (AMR)

AF:

0.298

AC:

4550

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

1379

AN:

3466

East Asian (EAS)

AF:

0.223

AC:

1150

AN:

5166

South Asian (SAS)

AF:

0.133

AC:

644

AN:

4826

European-Finnish (FIN)

AF:

0.218

AC:

2308

AN:

10590

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.251

AC:

17086

AN:

67972

Other (OTH)

AF:

0.306

AC:

647

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1590

3180

4771

6361

7951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.272

Hom.:

742

Bravo

AF:

0.298

Asia WGS

AF:

0.199

AC:

694

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.3

(source)

DANN

Benign

0.78

PhyloP100

0.044

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