rs7413823

Variant names:

• chr1-65558033-A-G
• rs7413823
• NM_002303.6:c.-20-7513A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-65558033-A-G
• chr1-65558033-A-T

Variant summary

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

The NM_002303.6(LEPR):​c.-20-7513A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 151,828 control chromosomes in the GnomAD database, including 38,757 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 0.71 (38757 hom., cov: 32)
• Consequence: LEPR NM_002303.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.624
• Publications: 0 publications found

Genes affected

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 Gene-Disease associations (from GenCC):

• obesity due to leptin receptor gene deficiency

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LEPR	NM_002303.6	c.-20-7513A>G		intron_variant	Intron 2 of 19	ENST00000349533.11	NP_002294.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LEPR	ENST00000349533.11	c.-20-7513A>G		intron_variant	Intron 2 of 19	1	NM_002303.6	ENSP00000330393.7

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107029 AN: 151710 Hom.: 38723 Cov.: 32

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.869

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.706 AC: 107115 AN: 151828 Hom.: 38757 Cov.: 32 AF XY: 0.702 AC XY: 52080 AN XY: 74186

African (AFR) AF: 0.763 AC: 31606 AN: 41402

American (AMR) AF: 0.706 AC: 10770 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2863 AN: 3470

East Asian (EAS) AF: 0.175 AC: 905 AN: 5178

South Asian (SAS) AF: 0.799 AC: 3855 AN: 4822

European-Finnish (FIN) AF: 0.619 AC: 6505 AN: 10508

Middle Eastern (MID) AF: 0.869 AC: 252 AN: 290

European-Non Finnish (NFE) AF: 0.708 AC: 48086 AN: 67882

Other (OTH) AF: 0.726 AC: 1529 AN: 2106

Alfa AF: 0.732 Hom.: 8971

Bravo AF: 0.711

Asia WGS AF: 0.569 AC: 1981 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.6
DANN	Benign	0.69
PhyloP100		0.62
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: rs7413823; hg19: chr1-66023716;