dbSNP rs10895068: PGR-AS1:n.407C>T (chr11-101129483-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000632820.1(PGR-AS1):n.407C>T 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 0.037 in 238,568 control chromosomes in the GnomAD database, including 240 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 0.036 ( 142 hom., cov: 31)

Exomes 𝑓: 0.039 ( 98 hom. )

Consequence

PGR-AS1
ENST00000632820.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.305

Publications

104 publications found

Variant links:

Genes affected

PGR-AS1 (HGNC:52650): (PGR antisense RNA 1)

PGR-AS1 links:

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=-0.57).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4 link	c.-413G>A		5_prime_UTR_variant	Exon 1 of 8	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10 link	c.-413G>A		5_prime_UTR_variant	Exon 1 of 8	1	NM_000926.4	ENSP00000325120.5

Frequencies

GnomAD3 genomes

AF:

0.0358

AC:

5445

AN:

152078

Hom.:

142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00987

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0322

Gnomad ASJ

AF:

0.0363

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.0375

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0569

Gnomad OTH

AF:

0.0263

GnomAD4 exome

AF:

0.0392

AC:

3389

AN:

86372

Hom.:

Cov.:

AF XY:

0.0383

AC XY:

1564

AN XY:

40830

show subpopulations

African (AFR)

AF:

0.0117

AC:

AN:

3684

American (AMR)

AF:

0.0238

AC:

AN:

3652

Ashkenazi Jewish (ASJ)

AF:

0.0352

AC:

166

AN:

4712

East Asian (EAS)

AF:

0.000289

AC:

AN:

10382

South Asian (SAS)

AF:

0.00514

AC:

AN:

1362

European-Finnish (FIN)

AF:

0.0376

AC:

AN:

1090

Middle Eastern (MID)

AF:

0.00

AC:

AN:

430

European-Non Finnish (NFE)

AF:

0.0510

AC:

2779

AN:

54484

Other (OTH)

AF:

0.0400

AC:

263

AN:

6576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

169

338

506

675

844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0358

AC:

5445

AN:

152196

Hom.:

142

Cov.:

AF XY:

0.0331

AC XY:

2460

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00984

AC:

409

AN:

41558

American (AMR)

AF:

0.0321

AC:

491

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0363

AC:

126

AN:

3472

East Asian (EAS)

AF:

0.000582

AC:

AN:

5152

South Asian (SAS)

AF:

0.0108

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0375

AC:

397

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0569

AC:

3866

AN:

67980

Other (OTH)

AF:

0.0261

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

273

546

818

1091

1364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0439

Hom.:

Bravo

AF:

0.0335

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.3

(source)

DANN

Benign

0.91

PhyloP100

0.30

PromoterAI

-0.0036

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(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