rs7513047

Positions:

• chr1-65484657-G-A

Variant summary

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

The NM_002303.6(LEPR):​c.-21+59279G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,094 control chromosomes in the GnomAD database, including 10,327 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 0.33 (10327 hom., cov: 32)
• Consequence: LEPR NM_002303.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEPR	NM_002303.6	c.-21+59279G>A		intron_variant		ENST00000349533.11	NP_002294.2
LEPR	NM_001003679.3	c.-21+59279G>A		intron_variant			NP_001003679.1
LEPR	NM_001003680.3	c.-21+59279G>A		intron_variant			NP_001003680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEPR	ENST00000349533.11	c.-21+59279G>A		intron_variant		1	NM_002303.6	ENSP00000330393	P4
LEPR	ENST00000371059.7	c.-21+59279G>A		intron_variant		1		ENSP00000360098
LEPR	ENST00000371060.7	c.-21+59279G>A		intron_variant		1		ENSP00000360099	A1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49590 AN: 151976 Hom.: 10332 Cov.: 32

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.0291

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.326 AC: 49585 AN: 152094 Hom.: 10327 Cov.: 32 AF XY: 0.321 AC XY: 23831 AN XY: 74346

Gnomad4 AFR AF: 0.0873

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.0294

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.357

Alfa AF: 0.442 Hom.: 15574

Bravo AF: 0.315

Asia WGS AF: 0.149 AC: 518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.44

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: rs7513047; hg19: chr1-65950340;