rs1137101
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002303.6(LEPR):c.668A>G(p.Gln223Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151632 control chromosomes in the gnomAD Genomes database, including 20042 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (β β ).
Frequency
Genomes: π 0.50 ( 20042 hom., cov: 31)
Exomes π: 0.51 ( 33913 hom. )
Consequence
LEPR
NM_002303.6 missense
NM_002303.6 missense
Scores
2
15
Clinical Significance
Conservation
PhyloP100: 2.89
Links
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=7.772684E-7).
BP6
?
Variant 1-65592830-A-G is Benign according to our data. Variant chr1-65592830-A-G is described in ClinVar as [Benign]. Clinvar id is 8521. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-65592830-A-G is described in Lovd as [Benign].
BA1
?
GnomAd highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LEPR | NM_002303.6 | c.668A>G | p.Gln223Arg | missense_variant | 6/20 | ENST00000349533.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LEPR | ENST00000349533.11 | c.668A>G | p.Gln223Arg | missense_variant | 6/20 | 1 | NM_002303.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.503 AC: 76329AN: 151632Hom.: 20042 Cov.: 31
GnomAD3 genomes
AF:
AC:
76329
AN:
151632
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.506 AC: 126767AN: 250536Hom.: 33913 AF XY: 0.499 AC XY: 67578AN XY: 135420
GnomAD3 exomes
AF:
AC:
126767
AN:
250536
Hom.:
AF XY:
AC XY:
67578
AN XY:
135420
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.466 AC: 680577AN: 1460762Hom.: 163870 AF XY: 0.464 AC XY: 337258AN XY: 726694
GnomAD4 exome
AF:
AC:
680577
AN:
1460762
Hom.:
AF XY:
AC XY:
337258
AN XY:
726694
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
2471
ESP6500EA
AF:
AC:
3906
ExAC
AF:
AC:
61850
Asia WGS
AF:
AC:
2362
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics Inc | Jul 26, 2017 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 09, 2018 | This variant is associated with the following publications: (PMID: 9175732, 26150085, 24985001, 32429577, 24051404, 23954230, 23429533, 12634434, 28386678, 22333091, 25114924, 24631298, 11354636, 24146750, 24743494, 21233812, 18997673, 20874424, 19344216, 21698367, 25516614, 18204169, 22127368, 18855010, 21393862, 21207066, 20183928, 22734460, 23769971, 19017403, 21159927, 23026206, 23966608, 19427969) - |
LEPTIN RECEPTOR POLYMORPHISM Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Nov 01, 2007 | - - |
Monogenic Non-Syndromic Obesity Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Obesity due to leptin receptor gene deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T;T;T;.
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;L;L
MutationTaster
Benign
P;P;P;P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;.;N
REVEL
Benign
Sift
Benign
T;T;T;T;.;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
P;B;B;.;B;.
Vest4
MPC
0.12
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at