chr1-65619891-T-A
Position:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_002303.6(LEPR):c.2396-37T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,471,512 control chromosomes in the GnomAD database, including 129,980 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.46 ( 17196 hom., cov: 32)
Exomes 𝑓: 0.40 ( 112784 hom. )
Consequence
LEPR
NM_002303.6 intron
NM_002303.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.287
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 1-65619891-T-A is Benign according to our data. Variant chr1-65619891-T-A is described in ClinVar as [Benign]. Clinvar id is 1262802.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LEPR | NM_002303.6 | c.2396-37T>A | intron_variant | ENST00000349533.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LEPR | ENST00000349533.11 | c.2396-37T>A | intron_variant | 1 | NM_002303.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.463 AC: 70321AN: 151878Hom.: 17159 Cov.: 32
GnomAD3 genomes
AF:
AC:
70321
AN:
151878
Hom.:
Cov.:
32
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:
GnomAD3 exomes AF: 0.463 AC: 113631AN: 245322Hom.: 28495 AF XY: 0.455 AC XY: 60469AN XY: 132776
GnomAD3 exomes
AF:
AC:
113631
AN:
245322
Hom.:
AF XY:
AC XY:
60469
AN XY:
132776
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.401 AC: 529394AN: 1319516Hom.: 112784 Cov.: 20 AF XY: 0.402 AC XY: 266761AN XY: 664218
GnomAD4 exome
AF:
AC:
529394
AN:
1319516
Hom.:
Cov.:
20
AF XY:
AC XY:
266761
AN XY:
664218
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.463 AC: 70414AN: 151996Hom.: 17196 Cov.: 32 AF XY: 0.470 AC XY: 34947AN XY: 74286
GnomAD4 genome
AF:
AC:
70414
AN:
151996
Hom.:
Cov.:
32
AF XY:
AC XY:
34947
AN XY:
74286
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.:
Bravo
AF:
Asia WGS
AF:
AC:
2165
AN:
3472
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 | Sep 05, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at