GeneBe

rs2186248

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002303.6(LEPR):​c.370+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LEPR
NM_002303.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.452

Publications

6 publications found
Variant links:
Genes affected
LEPR (HGNC:6554): (leptin receptor) The protein encoded by this gene belongs to the gp130 family of cytokine receptors that are known to stimulate gene transcription via activation of cytosolic STAT proteins. This protein is a receptor for leptin (an adipocyte-specific hormone that regulates body weight), and is involved in the regulation of fat metabolism, as well as in a novel hematopoietic pathway that is required for normal lymphopoiesis. Mutations in this gene have been associated with obesity and pituitary dysfunction. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. It is noteworthy that this gene and LEPROT gene (GeneID:54741) share the same promoter and the first 2 exons, however, encode distinct proteins (PMID:9207021).[provided by RefSeq, Nov 2010]
LEPR Gene-Disease associations (from GenCC):
  • obesity due to leptin receptor gene deficiency
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002303.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
LEPR
NM_002303.6
MANE Select
c.370+16G>A
intron
N/ANP_002294.2
LEPR
NM_001003680.3
c.370+16G>A
intron
N/ANP_001003680.1
LEPR
NM_001198687.2
c.370+16G>A
intron
N/ANP_001185616.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
LEPR
ENST00000349533.11
TSL:1 MANE Select
c.370+16G>A
intron
N/AENSP00000330393.7
LEPR
ENST00000371059.7
TSL:1
c.370+16G>A
intron
N/AENSP00000360098.3
LEPR
ENST00000344610.12
TSL:1
c.370+16G>A
intron
N/AENSP00000340884.8

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1373100
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
674334
African (AFR)
AF:
0.00
AC:
0
AN:
30488
American (AMR)
AF:
0.00
AC:
0
AN:
30554
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
20908
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38888
South Asian (SAS)
AF:
0.00
AC:
0
AN:
69356
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49666
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4922
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1071736
Other (OTH)
AF:
0.00
AC:
0
AN:
56582
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
1.8
DANN
Benign
0.78
PhyloP100
-0.45
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs2186248; hg19: chr1-66036501; API