rs3793162

Variant names:

• chr7-128254015-G-A
• rs3793162
• NM_000230.3:c.145-389G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-128254015-G-A
• chr7-128254015-G-C
• chr7-128254015-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000230.3(LEP):​c.145-389G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 151,912 control chromosomes in the GnomAD database, including 479 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.049 (479 hom., cov: 31)
• Consequence: LEP NM_000230.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• obesity due to congenital leptin deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ENSG00000289434 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000230.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEP	NM_000230.3	MANE Select	c.145-389G>A		intron	N/A	NP_000221.1	P41159

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEP	ENST00000308868.5	TSL:1 MANE Select	c.145-389G>A		intron	N/A	ENSP00000312652.4	P41159
	LEP	ENST00000965599.1		c.145-392G>A		intron	N/A	ENSP00000635658.1
	ENSG00000289434	ENST00000785131.1		n.168+9347C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0486 AC: 7374 AN: 151794 Hom.: 478 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0269

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.0520

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00213

Gnomad OTH AF: 0.0499

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0486 AC: 7385 AN: 151912 Hom.: 479 Cov.: 31 AF XY: 0.0476 AC XY: 3532 AN XY: 74258

African (AFR) AF: 0.150 AC: 6206 AN: 41274

American (AMR) AF: 0.0268 AC: 409 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3468

East Asian (EAS) AF: 0.0517 AC: 267 AN: 5164

South Asian (SAS) AF: 0.0212 AC: 102 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00213 AC: 145 AN: 67982

Other (OTH) AF: 0.0494 AC: 104 AN: 2106

Alfa AF: 0.00201 Hom.: 3

Bravo AF: 0.0561

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.057
DANN	Benign	0.45
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3793162; hg19: chr7-127894068;