1-65565843-TCTCA-T

Position:

• chr1-65565843-TCTCA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002303.6(LEPR):​c.40+240_40+243del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0064 (12 hom., cov: 11)
• Consequence: LEPR NM_002303.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.129

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 -10 ACMG points.

• BP6: Variant 1-65565843-TCTCA-T is Benign according to our data. Variant chr1-65565843-TCTCA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1203311.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00643 (968/150510) while in subpopulation NFE AF= 0.0103 (697/67684). AF 95% confidence interval is 0.00966. There are 12 homozygotes in gnomad4. There are 449 alleles in male gnomad4 subpopulation. Median coverage is 11. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEPR	NM_002303.6	c.40+240_40+243del		intron_variant		ENST00000349533.11	NP_002294.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEPR	ENST00000349533.11	c.40+240_40+243del		intron_variant		1	NM_002303.6	ENSP00000330393	P4

Frequencies

GnomAD3 genomes AF: 0.00641 AC: 964 AN: 150404 Hom.: 12 Cov.: 11

Gnomad AFR AF: 0.00231

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.000396

Gnomad SAS AF: 0.00462

Gnomad FIN AF: 0.000967

Gnomad MID AF: 0.0256

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.00975

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

GnomAD4 genome AF: 0.00643 AC: 968 AN: 150510 Hom.: 12 Cov.: 11 AF XY: 0.00611 AC XY: 449 AN XY: 73476

Gnomad4 AFR AF: 0.00232

Gnomad4 AMR AF: 0.00490

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.000397

Gnomad4 SAS AF: 0.00526

Gnomad4 FIN AF: 0.000967

Gnomad4 NFE AF: 0.0103

Gnomad4 OTH AF: 0.00965

Alfa AF: 0.00780 Hom.: 0

Bravo AF: 0.00628

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs1440292866; hg19: chr1-66031526;