Genetic Variant PGR:c.2213-105T>A (chr11-101051673-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.2213-105T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 814,666 control chromosomes in the GnomAD database, including 230,943 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 0.72 ( 40424 hom., cov: 33)

Exomes 𝑓: 0.76 ( 190519 hom. )

Consequence

PGR
NM_000926.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.30

Publications

12 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=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4 link	c.2213-105T>A		intron_variant	Intron 4 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.2213-105T>A		intron_variant	Intron 4 of 7	1	NM_000926.4	ENSP00000325120.5		P06401-1

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110164

AN:

151986

Hom.:

40380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.640

Gnomad AMI

AF:

0.623

Gnomad AMR

AF:

0.782

Gnomad ASJ

AF:

0.764

Gnomad EAS

AF:

0.996

Gnomad SAS

AF:

0.766

Gnomad FIN

AF:

0.780

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.731

Gnomad OTH

AF:

0.732

GnomAD4 exome

AF:

0.755

AC:

500291

AN:

662562

Hom.:

190519

AF XY:

0.753

AC XY:

267206

AN XY:

355086

show subpopulations

African (AFR)

AF:

0.643

AC:

11476

AN:

17846

American (AMR)

AF:

0.841

AC:

32517

AN:

38678

Ashkenazi Jewish (ASJ)

AF:

0.762

AC:

15355

AN:

20158

East Asian (EAS)

AF:

0.999

AC:

35526

AN:

35558

South Asian (SAS)

AF:

0.751

AC:

49860

AN:

66368

European-Finnish (FIN)

AF:

0.781

AC:

39385

AN:

50444

Middle Eastern (MID)

AF:

0.702

AC:

1777

AN:

2530

European-Non Finnish (NFE)

AF:

0.728

AC:

289408

AN:

397394

Other (OTH)

AF:

0.744

AC:

24987

AN:

33586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

5793

11587

17380

23174

28967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2918

5836

8754

11672

14590

<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:

0.725

AC:

110262

AN:

152104

Hom.:

40424

Cov.:

AF XY:

0.729

AC XY:

54223

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.640

AC:

26550

AN:

41476

American (AMR)

AF:

0.783

AC:

11955

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.764

AC:

2651

AN:

3470

East Asian (EAS)

AF:

0.996

AC:

5165

AN:

5184

South Asian (SAS)

AF:

0.767

AC:

3703

AN:

4826

European-Finnish (FIN)

AF:

0.780

AC:

8245

AN:

10574

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.731

AC:

49669

AN:

67984

Other (OTH)

AF:

0.734

AC:

1552

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1542

3084

4626

6168

7710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.664

Hom.:

2023

Bravo

AF:

0.722

Asia WGS

AF:

0.896

AC:

3113

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

2.0

(source)

DANN

Benign

0.35

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