Variant rs12145690 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001198681.2(LEPROT):c.-87A>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,532,774 control chromosomes in the GnomAD database, including 178,993 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 16920 hom., cov: 32)

Exomes 𝑓: 0.48 ( 162073 hom. )

Consequence

LEPROT
NM_001198681.2 splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.466

Variant links:

Genes affected

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:

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:):

LEPROT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 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.-97+590A>C		intron_variant		ENST00000349533.11	NP_002294.2	P48357-1
LEPROT	NM_017526.5 linkuse as main transcript	c.16+590A>C		intron_variant		ENST00000371065.9	NP_059996.1	O15243

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEPR	ENST00000349533.11 linkuse as main transcript	c.-97+590A>C		intron_variant		1	NM_002303.6	ENSP00000330393.7		P48357-1
LEPROT	ENST00000371065.9 linkuse as main transcript	c.16+590A>C		intron_variant		1	NM_017526.5	ENSP00000360104.4		O15243

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70597

AN:

151904

Hom.:

16915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.413

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.451

Gnomad EAS

AF:

0.857

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.471

GnomAD4 exome

AF:

0.478

AC:

660619

AN:

1380752

Hom.:

162073

Cov.:

AF XY:

0.481

AC XY:

327765

AN XY:

681022

show subpopulations

Gnomad4 AFR exome

AF:

0.410

Gnomad4 AMR exome

AF:

0.491

Gnomad4 ASJ exome

AF:

0.466

Gnomad4 EAS exome

AF:

0.857

Gnomad4 SAS exome

AF:

0.577

Gnomad4 FIN exome

AF:

0.479

Gnomad4 NFE exome

AF:

0.460

Gnomad4 OTH exome

AF:

0.485

GnomAD4 genome

AF:

0.465

AC:

70624

AN:

152022

Hom.:

16920

Cov.:

AF XY:

0.470

AC XY:

34945

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.412

Gnomad4 AMR

AF:

0.461

Gnomad4 ASJ

AF:

0.451

Gnomad4 EAS

AF:

0.857

Gnomad4 SAS

AF:

0.589

Gnomad4 FIN

AF:

0.475

Gnomad4 NFE

AF:

0.457

Gnomad4 OTH

AF:

0.472

Alfa

AF:

0.464

Hom.:

28032

Bravo

AF:

0.459

Asia WGS

AF:

0.653

AC:

2273

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.9

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over