Variant 7-128254252-G-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 NM_000230.3(LEP):c.145-152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 909,420 control chromosomes in the GnomAD database, including 93,545 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 12628 hom., cov: 32)

Exomes 𝑓: 0.45 ( 80917 hom. )

Consequence

LEP
NM_000230.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.54

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:

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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=-0.95).

BP6

Variant 7-128254252-G-A is Benign according to our data. Variant chr7-128254252-G-A is described in ClinVar as [Benign]. Clinvar id is 1247016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 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.145-152G>A		intron_variant		ENST00000308868.5	NP_000221.1
LEP	XM_005250340.6 linkuse as main transcript	c.145-155G>A		intron_variant			XP_005250397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEP	ENST00000308868.5 linkuse as main transcript	c.145-152G>A		intron_variant		1	NM_000230.3	ENSP00000312652	P1

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58183

AN:

151892

Hom.:

12620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.405

Gnomad EAS

AF:

0.734

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.462

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.384

GnomAD4 exome

AF:

0.450

AC:

340882

AN:

757412

Hom.:

80917

AF XY:

0.455

AC XY:

181354

AN XY:

398366

show subpopulations

Gnomad4 AFR exome

AF:

0.183

Gnomad4 AMR exome

AF:

0.411

Gnomad4 ASJ exome

AF:

0.414

Gnomad4 EAS exome

AF:

0.761

Gnomad4 SAS exome

AF:

0.519

Gnomad4 FIN exome

AF:

0.465

Gnomad4 NFE exome

AF:

0.433

Gnomad4 OTH exome

AF:

0.440

GnomAD4 genome

AF:

0.383

AC:

58212

AN:

152008

Hom.:

12628

Cov.:

AF XY:

0.391

AC XY:

29015

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.439

Gnomad4 ASJ

AF:

0.405

Gnomad4 EAS

AF:

0.735

Gnomad4 SAS

AF:

0.522

Gnomad4 FIN

AF:

0.462

Gnomad4 NFE

AF:

0.439

Gnomad4 OTH

AF:

0.389

Alfa

AF:

0.410

Hom.:

3569

Bravo

AF:

0.369

Asia WGS

AF:

0.623

AC:

2163

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	Apr 07, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.0050

DANN

Benign

0.54

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over