Variant rs1137101 details in Genebe, Genetics Data Aggregator

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 (★★).

Frequency

Genomes: 𝑓 0.50 ( 20042 hom., cov: 31)

Exomes 𝑓: 0.51 ( 33913 hom. )

Consequence

LEPR
NM_002303.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.89

Links

LEPR (HGNC:6554):

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 linkuse as main transcript	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 linkuse as main transcript	c.668A>G	p.Gln223Arg	missense_variant	6/20	1	NM_002303.6	P4	P48357-1

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76329

AN:

151632

Hom.:

20042

Cov.:

show subpopulations

Gnomad AFR

AF:

0.556

Gnomad AMI

AF:

0.272

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.879

Gnomad SAS

AF:

0.491

Gnomad FIN

AF:

0.594

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.470

GnomAD3 exomes

AF:

0.506

AC:

126767

AN:

250536

Hom.:

33913

AF XY:

0.499

AC XY:

67578

AN XY:

135420

show subpopulations

Gnomad AFR exome

AF:

0.562

Gnomad AMR exome

AF:

0.456

Gnomad ASJ exome

AF:

0.427

Gnomad EAS exome

AF:

0.881

Gnomad SAS exome

AF:

0.473

Gnomad FIN exome

AF:

0.598

Gnomad NFE exome

AF:

0.452

Gnomad OTH exome

AF:

0.472

GnomAD4 exome

AF:

0.466

AC:

680577

AN:

1460762

Hom.:

163870

AF XY:

0.464

AC XY:

337258

AN XY:

726694

show subpopulations

Gnomad4 AFR exome

AF:

0.559

Gnomad4 AMR exome

AF:

0.454

Gnomad4 ASJ exome

AF:

0.424

Gnomad4 EAS exome

AF:

0.873

Gnomad4 SAS exome

AF:

0.473

Gnomad4 FIN exome

AF:

0.600

Gnomad4 NFE exome

AF:

0.443

Gnomad4 OTH exome

AF:

0.477

Alfa

AF:

0.458

Hom.:

38572

Bravo

AF:

0.494

ESP6500AA

AF:

0.561

AC:

2471

ESP6500EA

AF:

0.454

AC:

3906

ExAC

AF:

0.509

AC:

61850

Asia WGS

AF:

0.680

AC:

2362

AN:

3478

EpiCase

AF:

0.429

EpiControl

AF:

0.425

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.094

Eigen_PC

Benign

0.016

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.53

T;.;T;T;T;.

MetaRNN

Benign

7.8e-7

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L;L;L;L;L

MutationTaster

Benign

0.62

P;P;P;P;P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.4

N;N;N;N;.;N

REVEL

Benign

0.034

Sift

Benign

0.22

T;T;T;T;.;T

Sift4G

Benign

0.19

T;T;T;T;T;T

Polyphen

0.83

P;B;B;.;B;.

Vest4

0.082

MPC

0.12

ClinPred

0.0063

GERP RS

3.7

Varity_R

0.14

gMVP

0.49

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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over