chr7-128250009-T-C

Position:

• chr7-128250009-T-C

Variant summary

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

The ENST00000308868.5(LEP):​c.-28-1982T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,050 control chromosomes in the GnomAD database, including 12,797 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 0.39 (12797 hom., cov: 32)
• Consequence: LEP ENST00000308868.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

Genes affected

LEP (HGNC:6553): (leptin) This gene encodes a protein that is secreted by white adipocytes into the circulation and plays a major role in the regulation of energy homeostasis. Circulating leptin binds to the leptin receptor in the brain, which activates downstream signaling pathways that inhibit feeding and promote energy expenditure. This protein also has several endocrine functions, and is involved in the regulation of immune and inflammatory responses, hematopoiesis, angiogenesis, reproduction, bone formation and wound healing. Mutations in this gene and its regulatory regions cause severe obesity and morbid obesity with hypogonadism in human patients. A mutation in this gene has also been linked to type 2 diabetes mellitus development. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEP	NM_000230.3	c.-28-1982T>C		intron_variant		ENST00000308868.5	NP_000221.1
LEP	XM_005250340.6	c.-28-1982T>C		intron_variant			XP_005250397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEP	ENST00000308868.5	c.-28-1982T>C		intron_variant		1	NM_000230.3	ENSP00000312652	P1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59141 AN: 151930 Hom.: 12800 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.389 AC: 59160 AN: 152050 Hom.: 12797 Cov.: 32 AF XY: 0.386 AC XY: 28699 AN XY: 74306

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.422

Alfa AF: 0.477 Hom.: 23498

Bravo AF: 0.385

Asia WGS AF: 0.261 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.72

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: rs11763517; hg19: chr7-127890062;