rs10789190

Variant names:

• chr1-65597897-G-A
• rs10789190
• NM_002303.6:c.850-763G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-65597897-G-A
• chr1-65597897-G-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.850-763G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,596 control chromosomes in the GnomAD database, including 20,059 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 0.50 (20059 hom., cov: 30)
• Consequence: LEPR NM_002303.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LEPR	NM_002303.6	c.850-763G>A		intron_variant	Intron 7 of 19	ENST00000349533.11	NP_002294.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LEPR	ENST00000349533.11	c.850-763G>A		intron_variant	Intron 7 of 19	1	NM_002303.6	ENSP00000330393.7

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76266 AN: 151478 Hom.: 20028 Cov.: 30

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.504 AC: 76348 AN: 151596 Hom.: 20059 Cov.: 30 AF XY: 0.510 AC XY: 37736 AN XY: 74064

African (AFR) AF: 0.558 AC: 23039 AN: 41286

American (AMR) AF: 0.440 AC: 6705 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1450 AN: 3460

East Asian (EAS) AF: 0.878 AC: 4523 AN: 5152

South Asian (SAS) AF: 0.489 AC: 2358 AN: 4820

European-Finnish (FIN) AF: 0.594 AC: 6217 AN: 10468

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.452 AC: 30708 AN: 67882

Other (OTH) AF: 0.476 AC: 998 AN: 2096

Alfa AF: 0.481 Hom.: 3528

Bravo AF: 0.494

Asia WGS AF: 0.680 AC: 2362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.15
PhyloP100		-0.83
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: rs10789190; hg19: chr1-66063580;