Variant rs3790438 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 NM_002303.6(LEPR):c.2396-86T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,018,134 control chromosomes in the GnomAD database, including 15,244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2485 hom., cov: 32)

Exomes 𝑓: 0.17 ( 12759 hom. )

Consequence

LEPR
NM_002303.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.902

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=-0.86).

BP6

Variant 1-65619842-T-A is Benign according to our data. Variant chr1-65619842-T-A is described in ClinVar as [Benign]. Clinvar id is 1247474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.2 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.2396-86T>A		intron_variant		ENST00000349533.11	NP_002294.2	P48357-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEPR	ENST00000349533.11 linkuse as main transcript	c.2396-86T>A		intron_variant		1	NM_002303.6	ENSP00000330393.7		P48357-1

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26614

AN:

152082

Hom.:

2485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.0600

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.179

GnomAD4 exome

AF:

0.168

AC:

145642

AN:

865934

Hom.:

12759

AF XY:

0.168

AC XY:

75824

AN XY:

450020

show subpopulations

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.175

Gnomad4 ASJ exome

AF:

0.218

Gnomad4 EAS exome

AF:

0.0821

Gnomad4 SAS exome

AF:

0.146

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.176

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

AF:

0.175

AC:

26627

AN:

152200

Hom.:

2485

Cov.:

AF XY:

0.173

AC XY:

12846

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.192

Gnomad4 AMR

AF:

0.206

Gnomad4 ASJ

AF:

0.221

Gnomad4 EAS

AF:

0.0604

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.174

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.160

Hom.:

257

Bravo

AF:

0.179

Asia WGS

AF:

0.0970

AC:

335

AN:

3470

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	clinical testing	GeneDx	Oct 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

DANN

Benign

0.62

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