rs7531110

Positions:

• chr1-65471382-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002303.6(LEPR):​c.-21+46004G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,014 control chromosomes in the GnomAD database, including 21,600 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 0.52 (21600 hom., cov: 32)
• Consequence: LEPR NM_002303.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEPR	NM_002303.6	c.-21+46004G>T		intron_variant		ENST00000349533.11	NP_002294.2
LEPR	NM_001003680.3	c.-21+46004G>T		intron_variant			NP_001003680.1
LEPR	NM_001003679.3	c.-21+46004G>T		intron_variant			NP_001003679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEPR	ENST00000349533.11	c.-21+46004G>T		intron_variant		1	NM_002303.6	ENSP00000330393.7
LEPR	ENST00000371059.7	c.-21+46004G>T		intron_variant		1		ENSP00000360098.3
LEPR	ENST00000371060.7	c.-21+46004G>T		intron_variant		1		ENSP00000360099.3

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79352 AN: 151896 Hom.: 21598 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.522 AC: 79368 AN: 152014 Hom.: 21600 Cov.: 32 AF XY: 0.515 AC XY: 38290 AN XY: 74308

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.545

Alfa AF: 0.571 Hom.: 5514

Bravo AF: 0.526

Asia WGS AF: 0.337 AC: 1178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.86
DANN	Benign	0.49

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

Other links and lift over

dbSNP: rs7531110; hg19: chr1-65937065;