Variant rs12067936 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.2673+37C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,592,948 control chromosomes in the GnomAD database, including 140,401 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17186 hom., cov: 32)

Exomes 𝑓: 0.40 ( 123215 hom. )

Consequence

LEPR
NM_002303.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0660

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:

LEPR (HGNC:):

LEPR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-65623018-C-A is Benign according to our data. Variant chr1-65623018-C-A is described in ClinVar as [Benign]. Clinvar id is 1183122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
LEPR	NM_002303.6 linkuse as main transcript	c.2673+37C>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.2673+37C>A		intron_variant		1	NM_002303.6	ENSP00000330393.7		P48357-1

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70255

AN:

151780

Hom.:

17149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.549

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.485

Gnomad ASJ

AF:

0.375

Gnomad EAS

AF:

0.870

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.435

GnomAD3 exomes

AF:

0.464

AC:

111844

AN:

240932

Hom.:

27937

AF XY:

0.457

AC XY:

59535

AN XY:

130406

show subpopulations

Gnomad AFR exome

AF:

0.557

Gnomad AMR exome

AF:

0.514

Gnomad ASJ exome

AF:

0.370

Gnomad EAS exome

AF:

0.872

Gnomad SAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.479

Gnomad NFE exome

AF:

0.375

Gnomad OTH exome

AF:

0.427

GnomAD4 exome

AF:

0.403

AC:

581230

AN:

1441050

Hom.:

123215

Cov.:

AF XY:

0.403

AC XY:

289389

AN XY:

717494

show subpopulations

Gnomad4 AFR exome

AF:

0.551

Gnomad4 AMR exome

AF:

0.506

Gnomad4 ASJ exome

AF:

0.376

Gnomad4 EAS exome

AF:

0.868

Gnomad4 SAS exome

AF:

0.464

Gnomad4 FIN exome

AF:

0.473

Gnomad4 NFE exome

AF:

0.370

Gnomad4 OTH exome

AF:

0.418

GnomAD4 genome

AF:

0.463

AC:

70348

AN:

151898

Hom.:

17186

Cov.:

AF XY:

0.470

AC XY:

34912

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.550

Gnomad4 AMR

AF:

0.485

Gnomad4 ASJ

AF:

0.375

Gnomad4 EAS

AF:

0.869

Gnomad4 SAS

AF:

0.462

Gnomad4 FIN

AF:

0.491

Gnomad4 NFE

AF:

0.378

Gnomad4 OTH

AF:

0.442

Alfa

AF:

0.358

Hom.:

2302

Bravo

AF:

0.465

Asia WGS

AF:

0.626

AC:

2175

AN:

3478

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	Sep 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.8

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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