Variant chr7-128252093-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000230.3(LEP):c.75A>G(p.Gln25=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,614,158 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 110 hom. )

Consequence

LEP
NM_000230.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.815

Variant links:

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]

LEP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 7-128252093-A-G is Benign according to our data. Variant chr7-128252093-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 778362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.815 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0057 (868/152284) while in subpopulation EAS AF= 0.0513 (265/5170). AF 95% confidence interval is 0.0462. There are 16 homozygotes in gnomad4. There are 449 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LEP	NM_000230.3 linkuse as main transcript	c.75A>G	p.Gln25=	synonymous_variant	2/3	ENST00000308868.5
LEP	XM_005250340.6 linkuse as main transcript	c.75A>G	p.Gln25=	synonymous_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LEP	ENST00000308868.5 linkuse as main transcript	c.75A>G	p.Gln25=	synonymous_variant	2/3	1	NM_000230.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00572

AC:

870

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00685

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.0254

Gnomad EAS

AF:

0.0515

Gnomad SAS

AF:

0.0189

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00775

AC:

1949

AN:

251488

Hom.:

AF XY:

0.00791

AC XY:

1075

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00732

Gnomad AMR exome

AF:

0.00211

Gnomad ASJ exome

AF:

0.0264

Gnomad EAS exome

AF:

0.0446

Gnomad SAS exome

AF:

0.0161

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00123

Gnomad OTH exome

AF:

0.00635

GnomAD4 exome

AF:

0.00381

AC:

5567

AN:

1461874

Hom.:

110

Cov.:

AF XY:

0.00419

AC XY:

3044

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00654

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.0275

Gnomad4 EAS exome

AF:

0.0466

Gnomad4 SAS exome

AF:

0.0158

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000605

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.00570

AC:

868

AN:

152284

Hom.:

Cov.:

AF XY:

0.00603

AC XY:

449

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00686

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.0254

Gnomad4 EAS

AF:

0.0513

Gnomad4 SAS

AF:

0.0187

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.00358

Hom.:

Bravo

AF:

0.00540

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 28, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

2.6

DANN

Benign

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over