chr1-65640261-C-T

Position:

• chr1-65640261-C-T

Variant summary

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

The NM_002303.6(LEPR):​c.*3246C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,948 control chromosomes in the GnomAD database, including 15,547 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 0.44 (15547 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: LEPR NM_002303.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEPR	NM_002303.6	c.*3246C>T		3_prime_UTR_variant	20/20	ENST00000349533.11	NP_002294.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEPR	ENST00000349533.11	c.*3246C>T		3_prime_UTR_variant	20/20	1	NM_002303.6	ENSP00000330393.7

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67012 AN: 151830 Hom.: 15509 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.419

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.442 AC: 67111 AN: 151948 Hom.: 15547 Cov.: 32 AF XY: 0.450 AC XY: 33439 AN XY: 74264

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.426

Alfa AF: 0.395 Hom.: 27964

Bravo AF: 0.440

Asia WGS AF: 0.624 AC: 2165 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.27
DANN	Benign	0.45

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: rs1892534; hg19: chr1-66105944;