11-2161302-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PM2PP5_Very_StrongBP4
The variant allele was found at a frequency of 0.0000287 in 313,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152022Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000372 AC: 6AN: 161264Hom.: 0 Cov.: 0 AF XY: 0.0000245 AC XY: 2AN XY: 81586
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152022Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74252
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Variant often referred to as c.-331 C>G using alternate nomenclature; Published functional studies demonstrate a damaging effect on promoter activity (Garin et al., 2010; Bonnefond et al., 2011); A different variant at this position (c.-152 C>A) has been reported as likely pathogenic at GeneDx in association with neonatal diabetes; Nucleotide substitution has no predicted effect on splicing and is not conserved across species; This variant is associated with the following publications: (PMID: 29305569, 24622368, 32252216, 21592955, 20133622, 29183106, 31441606, 32656923, 34101350, 35140529, 33852861, 34458657) -
This variant occurs in a non-coding region of the INS gene. It does not change the encoded amino acid sequence of the INS protein. This variant is present in population databases (rs748749585, gnomAD 0.1%). This variant has been observed in individuals with neonatal diabetes (PMID: 20133622). It has also been observed to segregate with disease in related individuals. This variant is also known as c.-331 C>G. ClinVar contains an entry for this variant (Variation ID: 431443). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects INS function (PMID: 21592955). For these reasons, this variant has been classified as Pathogenic. -
not specified Pathogenic:1
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Hyperproinsulinemia;C1852092:Type 1 diabetes mellitus 2;C3150617:Maturity-onset diabetes of the young type 10;C5394307:Diabetes mellitus, permanent neonatal 4 Pathogenic:1
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Diabetes mellitus Pathogenic:1
PS3,PS4,PM2 -
Diabetes mellitus, permanent neonatal 4 Benign:1
Potent mutations in the INS gene can cause early onset diabetes mellitus which is insulin dependent. May have poor response to sulfonylureas, mutations in this gene can cause beta cell destruction.rs748749585 variant is Prevalent in patients with Neonatal diabetes mellitus. However, the role of this particular variant is yet to be ascertained -
Permanent neonatal diabetes mellitus Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at