rs1042838

Variant summary

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

The NM_000926.4(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
NM_000926.4 missense

Scores

2
16

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]

Genome browser will be placed here

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
PGRNM_000926.4 linkuse as main transcriptc.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
PGRENST00000325455.10 linkuse as main transcriptc.1978G>T p.Val660Leu missense_variant 4/81 NM_000926.4 ENSP00000325120 P1P06401-1

Frequencies

GnomAD3 genomes
AF:
0.116
AC:
17607
AN:
152036
Hom.:
1325
Cov.:
32
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.:
33
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.:
32
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
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.12
T;.;.;T
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.20
FATHMM_MKL
Benign
0.46
N
LIST_S2
Benign
0.59
T;T;T;T
MetaRNN
Benign
0.0016
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L;.;.;.
MutationTaster
Benign
0.99
P;P;P
PrimateAI
Uncertain
0.53
T
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
T
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.

Other links and lift over

dbSNP: rs1042838; hg19: chr11-100933412; API