rs756571131
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_002303.6(LEPR):c.3495_3496delGT(p.Ter1166IlefsTer14) variant causes a frameshift, stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,154 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002303.6 frameshift, stop_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000362 AC: 9AN: 248412Hom.: 0 AF XY: 0.0000446 AC XY: 6AN XY: 134668
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461008Hom.: 0 AF XY: 0.00000825 AC XY: 6AN XY: 726834
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74330
ClinVar
Submissions by phenotype
not specified Uncertain:1
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LEPR-related disorder Uncertain:1
The LEPR c.3495_3496delGT variant is predicted to result in extension of the open reading frame (p.*1166Ileext*13). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.011% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
not provided Uncertain:1
This variant is present in population databases (rs756571131, gnomAD 0.01%). This sequence change disrupts the translational stop signal of the LEPR mRNA. It is expected to extend the length of the LEPR protein by 13 additional amino acid residues. This variant has not been reported in the literature in individuals affected with LEPR-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 435748). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at