Variant 1-65633330-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000349533.11(LEPR):c.2674-2861C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,379,294 control chromosomes in the GnomAD database, including 19,003 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1739 hom., cov: 32)

Exomes 𝑓: 0.16 ( 17264 hom. )

Consequence

LEPR
ENST00000349533.11 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.260

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-65633330-C-A is Benign according to our data. Variant chr1-65633330-C-A is described in ClinVar as [Benign]. Clinvar id is 1259804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
LEPR	NM_002303.6 linkuse as main transcript	c.2674-2861C>A	intron_variant		ENST00000349533.11	NP_002294.2
LEPR	NM_001003679.3 linkuse as main transcript	c.*161C>A	3_prime_UTR_variant	20/20		NP_001003679.1
LEPR	NM_001198689.2 linkuse as main transcript	c.*161C>A	3_prime_UTR_variant	19/19		NP_001185618.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEPR	ENST00000371060.7 linkuse as main transcript	c.*161C>A	3_prime_UTR_variant	20/20	1		ENSP00000360099	A1	P48357-2
LEPR	ENST00000616738.4 linkuse as main transcript	c.*161C>A	3_prime_UTR_variant	19/19	1		ENSP00000483390	A1	P48357-2
LEPR	ENST00000349533.11 linkuse as main transcript	c.2674-2861C>A	intron_variant		1	NM_002303.6	ENSP00000330393	P4	P48357-1

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20774

AN:

151896

Hom.:

1736

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0578

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.0598

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.152

GnomAD4 exome

AF:

0.165

AC:

202173

AN:

1227280

Hom.:

17264

Cov.:

AF XY:

0.165

AC XY:

98308

AN XY:

595664

show subpopulations

Gnomad4 AFR exome

AF:

0.0559

Gnomad4 AMR exome

AF:

0.174

Gnomad4 ASJ exome

AF:

0.217

Gnomad4 EAS exome

AF:

0.0831

Gnomad4 SAS exome

AF:

0.141

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.171

Gnomad4 OTH exome

AF:

0.160

GnomAD4 genome

AF:

0.137

AC:

20788

AN:

152014

Hom.:

1739

Cov.:

AF XY:

0.136

AC XY:

10088

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.0580

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.219

Gnomad4 EAS

AF:

0.0601

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.170

Hom.:

2335

Bravo

AF:

0.136

Asia WGS

AF:

0.0900

AC:

312

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.76

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