Genetic Variant LEPR:c.40+239_40+240insACAC (chr1-65565843-T-TCACA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.79

Publications

0 publications found

Variant links:

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]

LEPR Gene-Disease associations (from GenCC):

obesity due to leptin receptor gene deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

LEPR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002303.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LEPR	NM_002303.6	MANE Select	c.40+239_40+240insACAC	intron	N/A	NP_002294.2
LEPR	NM_001003680.3		c.40+239_40+240insACAC	intron	N/A	NP_001003680.1	P48357-3
LEPR	NM_001198687.2		c.40+239_40+240insACAC	intron	N/A	NP_001185616.1	P48357-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LEPR	ENST00000349533.11	TSL:1 MANE Select	c.40+238_40+239insCACA	intron	N/A	ENSP00000330393.7	P48357-1
LEPR	ENST00000371059.7	TSL:1	c.40+238_40+239insCACA	intron	N/A	ENSP00000360098.3	P48357-3
LEPR	ENST00000344610.12	TSL:1	c.40+238_40+239insCACA	intron	N/A	ENSP00000340884.8	P48357-4

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39284

AN:

150156

Hom.:

6035

Cov.:

show subpopulations

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.:

AF XY:

0.266

AC XY:

19487

AN XY:

73330

show subpopulations

African (AFR)

AF:

0.188

AC:

7665

AN:

40812

American (AMR)

AF:

0.260

AC:

3905

AN:

15046

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

503

AN:

3444

East Asian (EAS)

AF:

0.796

AC:

4006

AN:

5034

South Asian (SAS)

AF:

0.172

AC:

817

AN:

4746

European-Finnish (FIN)

AF:

0.361

AC:

3728

AN:

10316

Middle Eastern (MID)

AF:

0.128

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.266

AC:

17959

AN:

67600

Other (OTH)

AF:

0.251

AC:

519

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

1162

2324

3487

4649

5811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.112

Hom.:

248

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over