chr7-128254297-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_000230.3(LEP):c.145-107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 1,454,758 control chromosomes in the GnomAD database, including 1,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.033 ( 150 hom., cov: 32)
Exomes 𝑓: 0.040 ( 1265 hom. )
Consequence
LEP
NM_000230.3 intron
NM_000230.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.579
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=-0.78).
BP6
Variant 7-128254297-G-A is Benign according to our data. Variant chr7-128254297-G-A is described in ClinVar as [Benign]. Clinvar id is 1294302.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0331 (5046/152256) while in subpopulation NFE AF= 0.0491 (3341/68018). AF 95% confidence interval is 0.0477. There are 150 homozygotes in gnomad4. There are 2466 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 150 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LEP | NM_000230.3 | c.145-107G>A | intron_variant | ENST00000308868.5 | |||
LEP | XM_005250340.6 | c.145-110G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LEP | ENST00000308868.5 | c.145-107G>A | intron_variant | 1 | NM_000230.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0332 AC: 5050AN: 152140Hom.: 150 Cov.: 32
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GnomAD4 exome AF: 0.0405 AC: 52717AN: 1302502Hom.: 1265 AF XY: 0.0396 AC XY: 25956AN XY: 655718
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GnomAD4 genome AF: 0.0331 AC: 5046AN: 152256Hom.: 150 Cov.: 32 AF XY: 0.0331 AC XY: 2466AN XY: 74442
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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 | Apr 24, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at