rs10426094

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000208.4(INSR):​c.653-20592G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,208 control chromosomes in the GnomAD database, including 2,893 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 0.18 ( 2893 hom., cov: 33)

Consequence

INSR
NM_000208.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.644
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
INSRNM_000208.4 linkuse as main transcriptc.653-20592G>A intron_variant ENST00000302850.10 NP_000199.2
INSRNM_001079817.3 linkuse as main transcriptc.653-20592G>A intron_variant NP_001073285.1
INSRXM_011527988.3 linkuse as main transcriptc.653-20592G>A intron_variant XP_011526290.2
INSRXM_011527989.4 linkuse as main transcriptc.653-20592G>A intron_variant XP_011526291.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
INSRENST00000302850.10 linkuse as main transcriptc.653-20592G>A intron_variant 1 NM_000208.4 ENSP00000303830 A2P06213-1
INSRENST00000341500.9 linkuse as main transcriptc.653-20592G>A intron_variant 1 ENSP00000342838 P3P06213-2
INSRENST00000598216.1 linkuse as main transcriptn.628-20592G>A intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.184
AC:
28016
AN:
152090
Hom.:
2891
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0918
Gnomad AMI
AF:
0.135
Gnomad AMR
AF:
0.218
Gnomad ASJ
AF:
0.221
Gnomad EAS
AF:
0.0770
Gnomad SAS
AF:
0.196
Gnomad FIN
AF:
0.249
Gnomad MID
AF:
0.199
Gnomad NFE
AF:
0.228
Gnomad OTH
AF:
0.199
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.184
AC:
28031
AN:
152208
Hom.:
2893
Cov.:
33
AF XY:
0.185
AC XY:
13768
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.0919
Gnomad4 AMR
AF:
0.218
Gnomad4 ASJ
AF:
0.221
Gnomad4 EAS
AF:
0.0771
Gnomad4 SAS
AF:
0.196
Gnomad4 FIN
AF:
0.249
Gnomad4 NFE
AF:
0.228
Gnomad4 OTH
AF:
0.199
Alfa
AF:
0.222
Hom.:
8024
Bravo
AF:
0.179
Asia WGS
AF:
0.159
AC:
554
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
12
DANN
Benign
0.85

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

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

Other links and lift over

dbSNP: rs10426094; hg19: chr19-7205240; API