Variant 11-101062708-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000926.4(PGR):c.1951C>G(p.Leu651Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,613,656 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 7 hom. )

Consequence

PGR
NM_000926.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.15

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074652135).

BP6

Variant 11-101062708-G-C is Benign according to our data. Variant chr11-101062708-G-C is described in ClinVar as [Benign]. Clinvar id is 720193.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 309 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGR	NM_000926.4 linkuse as main transcript	c.1951C>G	p.Leu651Val	missense_variant	4/8	ENST00000325455.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGR	ENST00000325455.10 linkuse as main transcript	c.1951C>G	p.Leu651Val	missense_variant	4/8	1	NM_000926.4	P1	P06401-1

Frequencies

GnomAD3 genomes

AF:

0.00203

AC:

309

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00235

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00240

AC:

599

AN:

249450

Hom.:

AF XY:

0.00238

AC XY:

321

AN XY:

134834

show subpopulations

Gnomad AFR exome

AF:

0.000618

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0109

Gnomad NFE exome

AF:

0.00301

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00227

AC:

3319

AN:

1461458

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

1578

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0117

Gnomad4 NFE exome

AF:

0.00231

Gnomad4 OTH exome

AF:

0.00156

GnomAD4 genome

AF:

0.00203

AC:

309

AN:

152198

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

183

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0116

Gnomad4 NFE

AF:

0.00235

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00225

Hom.:

Bravo

AF:

0.00129

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00259

AC:

314

EpiCase

AF:

0.00240

EpiControl

AF:

0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.40

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.21

T;.;.;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.85

T;T;T;D

MetaRNN

Benign

0.0075

T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.3

M;.;.;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.5

N;N;.;.

REVEL

Benign

0.21

Sift

Benign

0.059

T;T;.;.

Sift4G

Benign

0.30

T;T;D;.

Polyphen

0.61

P;.;.;.

Vest4

0.17

MVP

0.74

ClinPred

0.015

GERP RS

1.9

Varity_R

0.066

gMVP

0.29

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over