1-65565843-T-TCACA

Position:

• chr1-65565843-T-TCACA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002303.6(LEPR):​c.40+239_40+240insACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (6034 hom., cov: 11)
• Consequence: LEPR NM_002303.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.79

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-T-TCACA is Benign according to our data. Variant chr1-65565843-T-TCACA is described in ClinVar as [Benign]. Clinvar id is 1286753.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEPR	NM_002303.6	c.40+239_40+240insACAC		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+239_40+240insACAC		intron_variant		1	NM_002303.6	ENSP00000330393	P4

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39284 AN: 150156 Hom.: 6035 Cov.: 11

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.125

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.262 AC: 39306 AN: 150264 Hom.: 6034 Cov.: 11 AF XY: 0.266 AC XY: 19487 AN XY: 73330

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.251

Alfa AF: 0.112 Hom.: 248

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 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs67805092; hg19: chr1-66031526;