GeneBe

rs3835070

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000208.4(INSR):​c.653-15_653-4delTCTCTCTCTCTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

INSR
NM_000208.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

Publications

4 publications found
Variant links:
Genes affected
INSR (HGNC:6091): (insulin receptor) This gene encodes a member of the receptor tyrosine kinase family of proteins. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form a heterotetrameric receptor. Binding of insulin or other ligands to this receptor activates the insulin signaling pathway, which regulates glucose uptake and release, as well as the synthesis and storage of carbohydrates, lipids and protein. Mutations in this gene underlie the inherited severe insulin resistance syndromes including type A insulin resistance syndrome, Donohue syndrome and Rabson-Mendenhall syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]
INSR Gene-Disease associations (from GenCC):
  • insulin-resistance syndrome type A
    Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
  • Donohue syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
  • hyperinsulinism due to INSR deficiency
    Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, Ambry Genetics
  • Rabson-Mendenhall syndrome
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
INSRNM_000208.4 linkc.653-15_653-4delTCTCTCTCTCTC splice_region_variant, intron_variant Intron 2 of 21 ENST00000302850.10 NP_000199.2
INSRNM_001079817.3 linkc.653-15_653-4delTCTCTCTCTCTC splice_region_variant, intron_variant Intron 2 of 20 NP_001073285.1
INSRXM_011527988.3 linkc.653-15_653-4delTCTCTCTCTCTC splice_region_variant, intron_variant Intron 2 of 21 XP_011526290.2
INSRXM_011527989.4 linkc.653-15_653-4delTCTCTCTCTCTC splice_region_variant, intron_variant Intron 2 of 20 XP_011526291.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
INSRENST00000302850.10 linkc.653-15_653-4delTCTCTCTCTCTC splice_region_variant, intron_variant Intron 2 of 21 1 NM_000208.4 ENSP00000303830.4
INSRENST00000341500.9 linkc.653-15_653-4delTCTCTCTCTCTC splice_region_variant, intron_variant Intron 2 of 20 1 ENSP00000342838.4
INSRENST00000598216.1 linkn.628-15_628-4delTCTCTCTCTCTC splice_region_variant, intron_variant Intron 2 of 9 1

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1233948
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
617966
African (AFR)
AF:
0.00
AC:
0
AN:
24826
American (AMR)
AF:
0.00
AC:
0
AN:
39560
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23124
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36488
South Asian (SAS)
AF:
0.00
AC:
0
AN:
70478
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
47250
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3920
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
937140
Other (OTH)
AF:
0.00
AC:
0
AN:
51162
GnomAD4 genome
Cov.:
0
Alfa
AF:
0.00
Hom.:
141
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.0

Splicing

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

Publications

Other links and lift over

dbSNP: rs3835070; hg19: chr19-7184651; API