dbSNP rs608995: PGR:c.*4114T>A (chr11-101035002-A-T) – 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.*4114T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 197,360 control chromosomes in the GnomAD database, including 7,146 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 0.27 ( 5664 hom., cov: 32)

Exomes 𝑓: 0.26 ( 1482 hom. )

Consequence

PGR
NM_000926.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.30

Publications

13 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=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4 link	c.*4114T>A		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.*4114T>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_000926.4	ENSP00000325120.5		P06401-1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40705

AN:

151982

Hom.:

5645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.391

Gnomad EAS

AF:

0.223

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.284

GnomAD4 exome

AF:

0.255

AC:

11548

AN:

45260

Hom.:

1482

Cov.:

AF XY:

0.254

AC XY:

5319

AN XY:

20932

show subpopulations

African (AFR)

AF:

0.322

AC:

634

AN:

1966

American (AMR)

AF:

0.275

AC:

332

AN:

1208

Ashkenazi Jewish (ASJ)

AF:

0.370

AC:

1066

AN:

2880

East Asian (EAS)

AF:

0.234

AC:

1735

AN:

7414

South Asian (SAS)

AF:

0.152

AC:

AN:

408

European-Finnish (FIN)

AF:

0.0625

AC:

AN:

Middle Eastern (MID)

AF:

0.228

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.243

AC:

6647

AN:

27336

Other (OTH)

AF:

0.269

AC:

1007

AN:

3740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

412

824

1237

1649

2061

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:

0.268

AC:

40782

AN:

152100

Hom.:

5664

Cov.:

AF XY:

0.263

AC XY:

19561

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.338

AC:

14024

AN:

41490

American (AMR)

AF:

0.282

AC:

4302

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.391

AC:

1357

AN:

3472

East Asian (EAS)

AF:

0.223

AC:

1155

AN:

5168

South Asian (SAS)

AF:

0.128

AC:

617

AN:

4822

European-Finnish (FIN)

AF:

0.217

AC:

2292

AN:

10584

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.238

AC:

16160

AN:

67982

Other (OTH)

AF:

0.286

AC:

604

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1545

3089

4634

6178

7723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.257

Hom.:

696

Bravo

AF:

0.279

Asia WGS

AF:

0.196

AC:

682

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.24

(source)

DANN

Benign

0.49

PhyloP100

-1.3

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