Variant rs2167270 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_000230.3(LEP):c.-39G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 154,068 control chromosomes in the GnomAD database, including 10,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10565 hom., cov: 33)

Exomes 𝑓: 0.34 ( 124 hom. )

Consequence

LEP
NM_000230.3 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.12

Variant links:

Genes affected

LEP (HGNC:6553): (leptin) This gene encodes a protein that is secreted by white adipocytes into the circulation and plays a major role in the regulation of energy homeostasis. Circulating leptin binds to the leptin receptor in the brain, which activates downstream signaling pathways that inhibit feeding and promote energy expenditure. This protein also has several endocrine functions, and is involved in the regulation of immune and inflammatory responses, hematopoiesis, angiogenesis, reproduction, bone formation and wound healing. Mutations in this gene and its regulatory regions cause severe obesity and morbid obesity with hypogonadism in human patients. A mutation in this gene has also been linked to type 2 diabetes mellitus development. [provided by RefSeq, Aug 2017]

LEP 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=-0.79).

BP6

Variant 7-128241296-G-A is Benign according to our data. Variant chr7-128241296-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 358814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEP	NM_000230.3 linkuse as main transcript	c.-39G>A		5_prime_UTR_variant	1/3	ENST00000308868.5	NP_000221.1
LEP	XM_005250340.6 linkuse as main transcript	c.-39G>A		5_prime_UTR_variant	1/3		XP_005250397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEP	ENST00000308868.5 linkuse as main transcript	c.-39G>A		5_prime_UTR_variant	1/3	1	NM_000230.3	ENSP00000312652	P1

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56252

AN:

151972

Hom.:

10557

Cov.:

show subpopulations

Gnomad AFR

AF:

0.408

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.370

Gnomad OTH

AF:

0.366

GnomAD4 exome

AF:

0.335

AC:

663

AN:

1978

Hom.:

124

Cov.:

AF XY:

0.337

AC XY:

361

AN XY:

1072

show subpopulations

Gnomad4 AFR exome

AF:

0.594

Gnomad4 AMR exome

AF:

0.417

Gnomad4 ASJ exome

AF:

0.462

Gnomad4 EAS exome

AF:

0.141

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.354

Gnomad4 NFE exome

AF:

0.344

Gnomad4 OTH exome

AF:

0.350

GnomAD4 genome

AF:

0.370

AC:

56309

AN:

152090

Hom.:

10565

Cov.:

AF XY:

0.366

AC XY:

27225

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.409

Gnomad4 AMR

AF:

0.378

Gnomad4 ASJ

AF:

0.350

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.342

Gnomad4 NFE

AF:

0.370

Gnomad4 OTH

AF:

0.364

Alfa

AF:

0.372

Hom.:

10793

Bravo

AF:

0.380

Asia WGS

AF:

0.238

AC:

830

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 21, 2020	This variant is associated with the following publications: (PMID: 23751306) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Monogenic Non-Syndromic Obesity

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Obesity due to congenital leptin deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.68

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