Variant 1-65425500-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002303.6(LEPR):c.-21+122T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 718,438 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.027 ( 147 hom., cov: 32)

Exomes 𝑓: 0.0077 ( 67 hom. )

Consequence

LEPR
NM_002303.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.214

Variant links:

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]

LEPR links:

LEPROT (HGNC:29477): (leptin receptor overlapping transcript) LEPROT is associated with the Golgi complex and endosomes and has a role in cell surface expression of growth hormone receptor (GHR; MIM 600946) and leptin receptor (OBR, or LEPR; MIM 601007), thereby altering receptor-mediated cell signaling (Couturier et al., 2007 [PubMed 18042720]; Touvier et al., 2009 [PubMed 19907080]).[supplied by OMIM, Jul 2010]

LEPROT links:

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=-0.88).

BP6

Variant 1-65425500-T-A is Benign according to our data. Variant chr1-65425500-T-A is described in ClinVar as [Benign]. Clinvar id is 1225396.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEPR	NM_002303.6 linkuse as main transcript	c.-21+122T>A		intron_variant		ENST00000349533.11	NP_002294.2
LEPROT	NM_017526.5 linkuse as main transcript	c.92+122T>A		intron_variant		ENST00000371065.9	NP_059996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEPR	ENST00000349533.11 linkuse as main transcript	c.-21+122T>A		intron_variant		1	NM_002303.6	ENSP00000330393	P4	P48357-1
LEPROT	ENST00000371065.9 linkuse as main transcript	c.92+122T>A		intron_variant		1	NM_017526.5	ENSP00000360104	P1

Frequencies

GnomAD3 genomes

AF:

0.0266

AC:

4051

AN:

152178

Hom.:

143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0799

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0188

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00510

Gnomad OTH

AF:

0.0234

GnomAD4 exome

AF:

0.00769

AC:

4354

AN:

566142

Hom.:

AF XY:

0.00783

AC XY:

2316

AN XY:

295974

show subpopulations

Gnomad4 AFR exome

AF:

0.0790

Gnomad4 AMR exome

AF:

0.00844

Gnomad4 ASJ exome

AF:

0.0229

Gnomad4 EAS exome

AF:

0.000142

Gnomad4 SAS exome

AF:

0.0167

Gnomad4 FIN exome

AF:

0.000708

Gnomad4 NFE exome

AF:

0.00448

Gnomad4 OTH exome

AF:

0.0147

GnomAD4 genome

AF:

0.0268

AC:

4083

AN:

152296

Hom.:

147

Cov.:

AF XY:

0.0256

AC XY:

1907

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0804

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.0216

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0186

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00510

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.0201

Hom.:

Bravo

AF:

0.0291

Asia WGS

AF:

0.0330

AC:

115

AN:

3478

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

May 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.9

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over