chr19-7126626-G-T
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS1
The NM_000208.4(INSR):c.2971C>A(p.Leu991Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000517 in 1,565,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000208.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INSR | NM_000208.4 | c.2971C>A | p.Leu991Ile | missense_variant | 16/22 | ENST00000302850.10 | |
INSR | NM_001079817.3 | c.2935C>A | p.Leu979Ile | missense_variant | 15/21 | ||
INSR | XM_011527988.3 | c.2968C>A | p.Leu990Ile | missense_variant | 16/22 | ||
INSR | XM_011527989.4 | c.2932C>A | p.Leu978Ile | missense_variant | 15/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INSR | ENST00000302850.10 | c.2971C>A | p.Leu991Ile | missense_variant | 16/22 | 1 | NM_000208.4 | A2 | |
INSR | ENST00000341500.9 | c.2935C>A | p.Leu979Ile | missense_variant | 15/21 | 1 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00275 AC: 419AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000485 AC: 86AN: 177380Hom.: 0 AF XY: 0.000435 AC XY: 41AN XY: 94254
GnomAD4 exome AF: 0.000277 AC: 391AN: 1413226Hom.: 0 Cov.: 31 AF XY: 0.000231 AC XY: 161AN XY: 698178
GnomAD4 genome AF: 0.00275 AC: 419AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.00270 AC XY: 201AN XY: 74468
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 31, 2018 | - - |
Insulin-resistant diabetes mellitus AND acanthosis nigricans Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Monogenic diabetes Benign:1
Benign, criteria provided, single submitter | research | Personalized Diabetes Medicine Program, University of Maryland School of Medicine | Mar 16, 2018 | ACMG criteria: PP3 (4 predictors), BP4 (6 predictors), BS2 (12 controls and 12 cases from T2DM), BS1 (1% MAF in 1000g and ExAC African, but disease frequency of AD form is 1 in 100,000) NOTE: called VUS by Chicago=benign - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Hyperinsulinism due to INSR deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetics and Molecular Pathology, SA Pathology | Sep 01, 2021 | - - |
INSR-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 18, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at