rs7248939

Variant summary

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

The ENST00000302850.10(INSR):​c.101-531C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 984,182 control chromosomes in the GnomAD database, including 61,881 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 0.37 ( 10586 hom., cov: 30)
Exomes 𝑓: 0.35 ( 51295 hom. )

Consequence

INSR
ENST00000302850.10 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.05
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=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
INSRNM_000208.4 linkuse as main transcriptc.101-531C>T intron_variant ENST00000302850.10 NP_000199.2
INSRNM_001079817.3 linkuse as main transcriptc.101-531C>T intron_variant NP_001073285.1
INSRXM_011527988.3 linkuse as main transcriptc.101-531C>T intron_variant XP_011526290.2
INSRXM_011527989.4 linkuse as main transcriptc.101-531C>T intron_variant XP_011526291.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
INSRENST00000302850.10 linkuse as main transcriptc.101-531C>T intron_variant 1 NM_000208.4 ENSP00000303830 A2P06213-1
INSRENST00000341500.9 linkuse as main transcriptc.101-531C>T intron_variant 1 ENSP00000342838 P3P06213-2
INSRENST00000598216.1 linkuse as main transcriptn.76-531C>T intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.369
AC:
55921
AN:
151616
Hom.:
10563
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.392
Gnomad AMI
AF:
0.493
Gnomad AMR
AF:
0.361
Gnomad ASJ
AF:
0.288
Gnomad EAS
AF:
0.605
Gnomad SAS
AF:
0.353
Gnomad FIN
AF:
0.344
Gnomad MID
AF:
0.354
Gnomad NFE
AF:
0.346
Gnomad OTH
AF:
0.361
GnomAD4 exome
AF:
0.349
AC:
290608
AN:
832448
Hom.:
51295
Cov.:
29
AF XY:
0.348
AC XY:
133756
AN XY:
384424
show subpopulations
Gnomad4 AFR exome
AF:
0.393
Gnomad4 AMR exome
AF:
0.387
Gnomad4 ASJ exome
AF:
0.274
Gnomad4 EAS exome
AF:
0.605
Gnomad4 SAS exome
AF:
0.359
Gnomad4 FIN exome
AF:
0.351
Gnomad4 NFE exome
AF:
0.347
Gnomad4 OTH exome
AF:
0.357
GnomAD4 genome
AF:
0.369
AC:
55978
AN:
151734
Hom.:
10586
Cov.:
30
AF XY:
0.370
AC XY:
27406
AN XY:
74130
show subpopulations
Gnomad4 AFR
AF:
0.392
Gnomad4 AMR
AF:
0.361
Gnomad4 ASJ
AF:
0.288
Gnomad4 EAS
AF:
0.605
Gnomad4 SAS
AF:
0.352
Gnomad4 FIN
AF:
0.344
Gnomad4 NFE
AF:
0.346
Gnomad4 OTH
AF:
0.367
Alfa
AF:
0.348
Hom.:
4915
Bravo
AF:
0.371
Asia WGS
AF:
0.503
AC:
1749
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.074
DANN
Benign
0.47

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: rs7248939; hg19: chr19-7268438; API