1-65565843-T-TCA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

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

Frequency

Genomes: 𝑓 0.016 ( 33 hom., cov: 11)

Consequence

LEPR
NM_002303.6 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.79
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 1-65565843-T-TCA is Benign according to our data. Variant chr1-65565843-T-TCA is described in ClinVar as [Likely_benign]. Clinvar id is 1187101.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.016 (2401/150368) while in subpopulation AFR AF= 0.03 (1227/40866). AF 95% confidence interval is 0.0286. There are 33 homozygotes in gnomad4. There are 1192 alleles in male gnomad4 subpopulation. Median coverage is 11. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LEPRNM_002303.6 linkc.40+239_40+240insAC intron_variant Intron 3 of 19 ENST00000349533.11 NP_002294.2 P48357-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LEPRENST00000349533.11 linkc.40+238_40+239insCA intron_variant Intron 3 of 19 1 NM_002303.6 ENSP00000330393.7 P48357-1

Frequencies

GnomAD3 genomes
AF:
0.0159
AC:
2396
AN:
150266
Hom.:
33
Cov.:
11
show subpopulations
Gnomad AFR
AF:
0.0299
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0112
Gnomad ASJ
AF:
0.00116
Gnomad EAS
AF:
0.00119
Gnomad SAS
AF:
0.00357
Gnomad FIN
AF:
0.0241
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0103
Gnomad OTH
AF:
0.0176
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0160
AC:
2401
AN:
150368
Hom.:
33
Cov.:
11
AF XY:
0.0162
AC XY:
1192
AN XY:
73396
show subpopulations
Gnomad4 AFR
AF:
0.0300
Gnomad4 AMR
AF:
0.0112
Gnomad4 ASJ
AF:
0.00116
Gnomad4 EAS
AF:
0.00119
Gnomad4 SAS
AF:
0.00358
Gnomad4 FIN
AF:
0.0241
Gnomad4 NFE
AF:
0.0103
Gnomad4 OTH
AF:
0.0174
Alfa
AF:
0.00308
Hom.:
248

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Aug 21, 2019
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs67805092; hg19: chr1-66031526; API