chr1-65493714-T-C

Position:

• chr1-65493714-T-C

Variant summary

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

The NM_002303.6(LEPR):​c.-21+68336T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 151,846 control chromosomes in the GnomAD database, including 25,156 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 0.57 (25156 hom., cov: 31)
• Consequence: LEPR NM_002303.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEPR	NM_002303.6	c.-21+68336T>C		intron_variant		ENST00000349533.11	NP_002294.2
LEPR	NM_001003679.3	c.-21+68336T>C		intron_variant			NP_001003679.1
LEPR	NM_001003680.3	c.-21+68336T>C		intron_variant			NP_001003680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEPR	ENST00000349533.11	c.-21+68336T>C		intron_variant		1	NM_002303.6	ENSP00000330393	P4
LEPR	ENST00000371059.7	c.-21+68336T>C		intron_variant		1		ENSP00000360098
LEPR	ENST00000371060.7	c.-21+68336T>C		intron_variant		1		ENSP00000360099	A1
	ENST00000429871.1	n.102-153T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86023 AN: 151728 Hom.: 25147 Cov.: 31

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.0791

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.717

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.567 AC: 86071 AN: 151846 Hom.: 25156 Cov.: 31 AF XY: 0.558 AC XY: 41426 AN XY: 74194

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.0794

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.581

Alfa AF: 0.594 Hom.: 4930

Bravo AF: 0.576

Asia WGS AF: 0.333 AC: 1161 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.094
DANN	Benign	0.43

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: rs1327120; hg19: chr1-65959397;