rs1805094
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002303.6(LEPR):āc.1968G>Cā(p.Lys656Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,611,922 control chromosomes in the GnomAD database, including 23,611 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.
Frequency
Consequence
NM_002303.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LEPR | NM_002303.6 | c.1968G>C | p.Lys656Asn | missense_variant | 14/20 | ENST00000349533.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LEPR | ENST00000349533.11 | c.1968G>C | p.Lys656Asn | missense_variant | 14/20 | 1 | NM_002303.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.175 AC: 26619AN: 151938Hom.: 2495 Cov.: 33
GnomAD3 exomes AF: 0.159 AC: 39679AN: 250258Hom.: 3351 AF XY: 0.160 AC XY: 21636AN XY: 135428
GnomAD4 exome AF: 0.167 AC: 243993AN: 1459864Hom.: 21117 Cov.: 33 AF XY: 0.167 AC XY: 121425AN XY: 726234
GnomAD4 genome ? AF: 0.175 AC: 26632AN: 152058Hom.: 2494 Cov.: 33 AF XY: 0.173 AC XY: 12848AN XY: 74330
ClinVar
Submissions by phenotype
Obesity due to leptin receptor gene deficiency Benign:4
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Jul 28, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 18, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 12, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 16, 2018 | This variant is associated with the following publications: (PMID: 20814201, 22530350, 23315873, 23266707, 18413223, 14970363, 20185531, 12006639, 9175732) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 19, 2017 | - - |
LEPTIN RECEPTOR POLYMORPHISM Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Jul 01, 2001 | - - |
Monogenic Non-Syndromic Obesity Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at