Variant rs41457646 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.*2205G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,552 control chromosomes in the GnomAD database, including 1,328 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1326 hom., cov: 32)

Exomes 𝑓: 0.11 ( 2 hom. )

Consequence

LEP
NM_000230.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00100

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=-0.85).

BP6

Variant 7-128256968-G-A is Benign according to our data. Variant chr7-128256968-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 358842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEP	NM_000230.3 link	c.*2205G>A		3_prime_UTR_variant	3/3	ENST00000308868.5	NP_000221.1	P41159A4D0Y8
LEP	XM_005250340.6 link	c.*2205G>A		3_prime_UTR_variant	3/3		XP_005250397.1	P41159

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEP	ENST00000308868.5 link	c.*2205G>A		3_prime_UTR_variant	3/3	1	NM_000230.3	ENSP00000312652.4		P41159

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17295

AN:

152106

Hom.:

1325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0299

Gnomad AMI

AF:

0.206

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.0997

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.117

GnomAD4 exome

AF:

0.113

AC:

AN:

328

Hom.:

Cov.:

AF XY:

0.115

AC XY:

AN XY:

192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.0600

Gnomad4 NFE exome

AF:

0.167

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.114

AC:

17302

AN:

152224

Hom.:

1326

Cov.:

AF XY:

0.116

AC XY:

8609

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0298

Gnomad4 AMR

AF:

0.156

Gnomad4 ASJ

AF:

0.152

Gnomad4 EAS

AF:

0.122

Gnomad4 SAS

AF:

0.245

Gnomad4 FIN

AF:

0.0997

Gnomad4 NFE

AF:

0.144

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.123

Hom.:

303

Bravo

AF:

0.112

Asia WGS

AF:

0.192

AC:

669

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not provided

Benign:1

Likely 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

-0.85

CADD

Benign

0.74

DANN

Benign

0.41

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