chr1-65565380-G-A

Position:

• chr1-65565380-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002303.6(LEPR):​c.-20-166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,976 control chromosomes in the GnomAD database, including 21,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.53 (21607 hom., cov: 32)
• Consequence: LEPR NM_002303.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.571

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 1-65565380-G-A is Benign according to our data. Variant chr1-65565380-G-A is described in ClinVar as [Benign]. Clinvar id is 1235035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEPR	NM_002303.6	c.-20-166G>A		intron_variant		ENST00000349533.11	NP_002294.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEPR	ENST00000349533.11	c.-20-166G>A		intron_variant		1	NM_002303.6	ENSP00000330393	P4

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79719 AN: 151856 Hom.: 21583 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.525 AC: 79793 AN: 151976 Hom.: 21607 Cov.: 32 AF XY: 0.529 AC XY: 39274 AN XY: 74270

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.505

Alfa AF: 0.505 Hom.: 8989

Bravo AF: 0.510

Asia WGS AF: 0.670 AC: 2323 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.083
DANN	Benign	0.64

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: rs6673324; hg19: chr1-66031063;