Variant chr11-101062681-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000325455.10(PGR):c.1978G>T(p.Val660Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,613,600 control chromosomes in the GnomAD database, including 19,162 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1324 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17838 hom. )

Consequence

PGR
ENST00000325455.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.708

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015742183).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGR	NM_000926.4 linkuse as main transcript	c.1978G>T	p.Val660Leu	missense_variant	4/8	ENST00000325455.10	NP_000917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGR	ENST00000325455.10 linkuse as main transcript	c.1978G>T	p.Val660Leu	missense_variant	4/8	1	NM_000926.4	ENSP00000325120	P1	P06401-1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17607

AN:

152036

Hom.:

1325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0301

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.0739

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.130

AC:

32533

AN:

250006

Hom.:

2561

AF XY:

0.130

AC XY:

17615

AN XY:

135084

show subpopulations

Gnomad AFR exome

AF:

0.0266

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.246

Gnomad EAS exome

AF:

0.0110

Gnomad SAS exome

AF:

0.0807

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.156

Gnomad OTH exome

AF:

0.153

GnomAD4 exome

AF:

0.151

AC:

220053

AN:

1461446

Hom.:

17838

Cov.:

AF XY:

0.148

AC XY:

107783

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.0229

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.0102

Gnomad4 SAS exome

AF:

0.0812

Gnomad4 FIN exome

AF:

0.157

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.148

GnomAD4 genome

AF:

0.116

AC:

17607

AN:

152154

Hom.:

1324

Cov.:

AF XY:

0.114

AC XY:

8469

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0300

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.250

Gnomad4 EAS

AF:

0.0116

Gnomad4 SAS

AF:

0.0738

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.160

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.151

Hom.:

4644

Bravo

AF:

0.111

TwinsUK

AF:

0.158

AC:

585

ALSPAC

AF:

0.148

AC:

570

ESP6500AA

AF:

0.0300

AC:

132

ESP6500EA

AF:

0.164

AC:

1414

ExAC

AF:

0.125

AC:

15211

Asia WGS

AF:

0.0550

AC:

192

AN:

3478

EpiCase

AF:

0.163

EpiControl

AF:

0.158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;.;.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.59

T;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.;.;.

MutationTaster

Benign

0.99

P;P;P

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.68

N;N;.;.

REVEL

Benign

0.21

Sift

Benign

0.12

T;T;.;.

Sift4G

Benign

0.34

T;T;T;.

Polyphen

0.0060

B;.;.;.

Vest4

0.10

MutPred

0.10

Gain of disorder (P = 0.1557);.;.;.;

ClinPred

0.0034

GERP RS

4.5

Varity_R

0.071

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over