11-101127464-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000926.4(PGR):c.1607A>C(p.Gln536Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00093 in 1,560,306 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00053 ( 7 hom. )

Consequence

PGR
NM_000926.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.863

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:

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

PGR-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048434734).

BP6

Variant 11-101127464-T-G is Benign according to our data. Variant chr11-101127464-T-G is described in ClinVar as [Benign]. Clinvar id is 716972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000525 (740/1408222) while in subpopulation AFR AF = 0.0175 (516/29478). AF 95% confidence interval is 0.0163. There are 7 homozygotes in GnomAdExome4. There are 329 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 711 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGR	NM_000926.4 link	c.1607A>C	p.Gln536Pro	missense_variant	Exon 1 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.1607A>C	p.Gln536Pro	missense_variant	Exon 1 of 8	1	NM_000926.4	ENSP00000325120.5		P06401-1

Frequencies

GnomAD3 genomes

AF:

0.00467

AC:

710

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000876

AC:

143

AN:

163246

AF XY:

0.000747

show subpopulations

Gnomad AFR exome

AF:

0.0175

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.000127

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000104

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000525

AC:

740

AN:

1408222

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

329

AN XY:

698036

show subpopulations

African (AFR)

AF:

0.0175

AC:

516

AN:

29478

American (AMR)

AF:

0.00131

AC:

AN:

38994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24640

East Asian (EAS)

AF:

0.00

AC:

AN:

34892

South Asian (SAS)

AF:

0.0000999

AC:

AN:

80076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48596

Middle Eastern (MID)

AF:

0.00115

AC:

AN:

5216

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

1088176

Other (OTH)

AF:

0.00191

AC:

111

AN:

58154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00468

AC:

711

AN:

152084

Hom.:

Cov.:

AF XY:

0.00455

AC XY:

338

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0159

AC:

659

AN:

41524

American (AMR)

AF:

0.00281

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5102

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67954

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

106

141

176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000668

Hom.:

Bravo

AF:

0.00578

ESP6500AA

AF:

0.00909

AC:

ESP6500EA

AF:

0.000280

AC:

ExAC

AF:

0.00103

AC:

117

Asia WGS

AF:

0.00116

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.11

T;.;T;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.70

T;T;T;T

MetaRNN

Benign

0.0048

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L;.;.

PhyloP100

0.86

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.6

N;N;.;.

REVEL

Benign

0.043

Sift

Benign

0.092

T;T;.;.

Sift4G

Benign

0.25

T;T;T;T

Polyphen

0.055

B;.;.;.

Vest4

0.25

MVP

0.40

ClinPred

0.021

GERP RS

2.9

PromoterAI

0.053

Neutral

(source)

Varity_R

0.35

gMVP

0.58

Mutation Taster

=95/5

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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11-101127464-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over