chr1-65565843-T-TCACACA
Position:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_002303.6(LEPR):c.40+239_40+240insACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.017 ( 37 hom., cov: 11)
Consequence
LEPR
NM_002303.6 intron
NM_002303.6 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.79
Genes affected
LEPR (HGNC:6554): (leptin receptor) The protein encoded by this gene belongs to the gp130 family of cytokine receptors that are known to stimulate gene transcription via activation of cytosolic STAT proteins. This protein is a receptor for leptin (an adipocyte-specific hormone that regulates body weight), and is involved in the regulation of fat metabolism, as well as in a novel hematopoietic pathway that is required for normal lymphopoiesis. Mutations in this gene have been associated with obesity and pituitary dysfunction. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. It is noteworthy that this gene and LEPROT gene (GeneID:54741) share the same promoter and the first 2 exons, however, encode distinct proteins (PMID:9207021).[provided by RefSeq, Nov 2010]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP6
Variant 1-65565843-T-TCACACA is Benign according to our data. Variant chr1-65565843-T-TCACACA is described in ClinVar as [Likely_benign]. Clinvar id is 1193475.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0173 (2611/150494) while in subpopulation AMR AF= 0.0275 (415/15080). AF 95% confidence interval is 0.0253. There are 37 homozygotes in gnomad4. There are 1225 alleles in male gnomad4 subpopulation. Median coverage is 11. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 37 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LEPR | NM_002303.6 | c.40+239_40+240insACACAC | intron_variant | ENST00000349533.11 | NP_002294.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LEPR | ENST00000349533.11 | c.40+239_40+240insACACAC | intron_variant | 1 | NM_002303.6 | ENSP00000330393 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0173 AC: 2605AN: 150388Hom.: 36 Cov.: 11
GnomAD3 genomes
AF:
AC:
2605
AN:
150388
Hom.:
Cov.:
11
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.0173 AC: 2611AN: 150494Hom.: 37 Cov.: 11 AF XY: 0.0167 AC XY: 1225AN XY: 73470
GnomAD4 genome
AF:
AC:
2611
AN:
150494
Hom.:
Cov.:
11
AF XY:
AC XY:
1225
AN XY:
73470
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 10, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at