rs9436738

Variant names:

• chr1-65422877-G-A
• rs9436738
• NM_002303.6:c.-97+2137G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-65422877-G-A
• chr1-65422877-G-C

Variant summary

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

The NM_002303.6(LEPR):​c.-97+2137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,184 control chromosomes in the GnomAD database, including 1,267 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 0.13 (1267 hom., cov: 32)
• Consequence: LEPR NM_002303.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• 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]

LEPROT (HGNC:29477): (leptin receptor overlapping transcript) LEPROT is associated with the Golgi complex and endosomes and has a role in cell surface expression of growth hormone receptor (GHR; MIM 600946) and leptin receptor (OBR, or LEPR; MIM 601007), thereby altering receptor-mediated cell signaling (Couturier et al., 2007 [PubMed 18042720]; Touvier et al., 2009 [PubMed 19907080]).[supplied by OMIM, Jul 2010]

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 (NFE) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002303.6. 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
	LEPR	NM_002303.6	MANE Select	c.-97+2137G>A		intron	N/A	NP_002294.2
	LEPROT	NM_017526.5	MANE Select	c.16+2137G>A		intron	N/A	NP_059996.1	O15243
	LEPR	NM_001003680.3		c.-97+2137G>A		intron	N/A	NP_001003680.1	P48357-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEPR	ENST00000349533.11	TSL:1 MANE Select	c.-97+2137G>A		intron	N/A	ENSP00000330393.7	P48357-1
	LEPROT	ENST00000371065.9	TSL:1 MANE Select	c.16+2137G>A		intron	N/A	ENSP00000360104.4	O15243
	LEPR	ENST00000371059.7	TSL:1	c.-97+2137G>A		intron	N/A	ENSP00000360098.3	P48357-3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19118 AN: 152066 Hom.: 1263 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0994

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.126 AC: 19152 AN: 152184 Hom.: 1267 Cov.: 32 AF XY: 0.123 AC XY: 9159 AN XY: 74394

African (AFR) AF: 0.136 AC: 5644 AN: 41494

American (AMR) AF: 0.0992 AC: 1518 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3472

East Asian (EAS) AF: 0.00522 AC: 27 AN: 5176

South Asian (SAS) AF: 0.0885 AC: 427 AN: 4826

European-Finnish (FIN) AF: 0.123 AC: 1305 AN: 10598

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9324 AN: 68006

Other (OTH) AF: 0.126 AC: 265 AN: 2108

Alfa AF: 0.131 Hom.: 281

Bravo AF: 0.124

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.63
DANN	Benign	0.68
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: rs9436738; hg19: chr1-65888560;