chr7-128254424-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_000230.3(LEP):c.165G>A(p.Gln55=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 1,613,584 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 1 hom. )
Consequence
LEP
NM_000230.3 synonymous
NM_000230.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.336
Genes affected
LEP (HGNC:6553): (leptin) This gene encodes a protein that is secreted by white adipocytes into the circulation and plays a major role in the regulation of energy homeostasis. Circulating leptin binds to the leptin receptor in the brain, which activates downstream signaling pathways that inhibit feeding and promote energy expenditure. This protein also has several endocrine functions, and is involved in the regulation of immune and inflammatory responses, hematopoiesis, angiogenesis, reproduction, bone formation and wound healing. Mutations in this gene and its regulatory regions cause severe obesity and morbid obesity with hypogonadism in human patients. A mutation in this gene has also been linked to type 2 diabetes mellitus development. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 7-128254424-G-A is Benign according to our data. Variant chr7-128254424-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 724209.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BP7
Synonymous conserved (PhyloP=0.336 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LEP | NM_000230.3 | c.165G>A | p.Gln55= | synonymous_variant | 3/3 | ENST00000308868.5 | |
LEP | XM_005250340.6 | c.162G>A | p.Gln54= | synonymous_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LEP | ENST00000308868.5 | c.165G>A | p.Gln55= | synonymous_variant | 3/3 | 1 | NM_000230.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000985 AC: 15AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000227 AC: 57AN: 251028Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135692
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GnomAD4 exome AF: 0.000131 AC: 191AN: 1461370Hom.: 1 Cov.: 32 AF XY: 0.000153 AC XY: 111AN XY: 727002
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GnomAD4 genome AF: 0.0000985 AC: 15AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74368
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Obesity due to congenital leptin deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 10, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at