rs10158579
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_002303.6(LEPR):c.-21+58995T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,156 control chromosomes in the GnomAD database, including 3,458 homozygotes. 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: 𝑓 0.19 ( 3458 hom., cov: 32)
Consequence
LEPR
NM_002303.6 intron
NM_002303.6 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.451
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]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LEPR | NM_002303.6 | c.-21+58995T>C | intron_variant | Intron 2 of 19 | ENST00000349533.11 | NP_002294.2 | ||
LEPR | NM_001003680.3 | c.-21+58995T>C | intron_variant | Intron 2 of 19 | NP_001003680.1 | |||
LEPR | NM_001003679.3 | c.-21+58995T>C | intron_variant | Intron 2 of 19 | NP_001003679.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LEPR | ENST00000349533.11 | c.-21+58995T>C | intron_variant | Intron 2 of 19 | 1 | NM_002303.6 | ENSP00000330393.7 | |||
LEPR | ENST00000371059.7 | c.-21+58995T>C | intron_variant | Intron 2 of 19 | 1 | ENSP00000360098.3 | ||||
LEPR | ENST00000371060.7 | c.-21+58995T>C | intron_variant | Intron 2 of 19 | 1 | ENSP00000360099.3 |
Frequencies
GnomAD3 genomes AF: 0.194 AC: 29428AN: 152038Hom.: 3459 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
29428
AN:
152038
Hom.:
Cov.:
32
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:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.193 AC: 29440AN: 152156Hom.: 3458 Cov.: 32 AF XY: 0.192 AC XY: 14294AN XY: 74372 show subpopulations
GnomAD4 genome
AF:
AC:
29440
AN:
152156
Hom.:
Cov.:
32
AF XY:
AC XY:
14294
AN XY:
74372
Gnomad4 AFR
AF:
AC:
0.327001
AN:
0.327001
Gnomad4 AMR
AF:
AC:
0.204058
AN:
0.204058
Gnomad4 ASJ
AF:
AC:
0.21684
AN:
0.21684
Gnomad4 EAS
AF:
AC:
0.0499422
AN:
0.0499422
Gnomad4 SAS
AF:
AC:
0.267206
AN:
0.267206
Gnomad4 FIN
AF:
AC:
0.0643032
AN:
0.0643032
Gnomad4 NFE
AF:
AC:
0.1336
AN:
0.1336
Gnomad4 OTH
AF:
AC:
0.194891
AN:
0.194891
Heterozygous variant carriers
0
1127
2254
3380
4507
5634
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
306
612
918
1224
1530
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
610
AN:
3476
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Mutation Taster
=100/0
polymorphism (auto)
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