7-128254354-C-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000230.3(LEP):c.145-50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,604,972 control chromosomes in the GnomAD database, including 637 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.039 ( 250 hom., cov: 32)
Exomes 𝑓: 0.012 ( 387 hom. )
Consequence
LEP
NM_000230.3 intron
NM_000230.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.44
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 Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 7-128254354-C-T is Benign according to our data. Variant chr7-128254354-C-T is described in ClinVar as [Benign]. Clinvar id is 1266247.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LEP | NM_000230.3 | c.145-50C>T | intron_variant | ENST00000308868.5 | |||
LEP | XM_005250340.6 | c.145-53C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LEP | ENST00000308868.5 | c.145-50C>T | intron_variant | 1 | NM_000230.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0394 AC: 5997AN: 152068Hom.: 248 Cov.: 32
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GnomAD3 exomes AF: 0.0192 AC: 4679AN: 243660Hom.: 129 AF XY: 0.0182 AC XY: 2411AN XY: 132274
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GnomAD4 exome AF: 0.0123 AC: 17874AN: 1452786Hom.: 387 Cov.: 31 AF XY: 0.0127 AC XY: 9163AN XY: 723106
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GnomAD4 genome AF: 0.0395 AC: 6009AN: 152186Hom.: 250 Cov.: 32 AF XY: 0.0388 AC XY: 2886AN XY: 74396
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 16, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at