rs3842752
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000207.3(INS):c.*9C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,609,784 control chromosomes in the GnomAD database, including 34,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.17 ( 2322 hom., cov: 33)
Exomes 𝑓: 0.20 ( 31767 hom. )
Consequence
INS
NM_000207.3 3_prime_UTR
NM_000207.3 3_prime_UTR
Scores
13
Clinical Significance
Conservation
PhyloP100: -5.12
Genes affected
INS (HGNC:6081): (insulin) This gene encodes insulin, a peptide hormone that plays a vital role in the regulation of carbohydrate and lipid metabolism. After removal of the precursor signal peptide, proinsulin is post-translationally cleaved into three peptides: the B chain and A chain peptides, which are covalently linked via two disulfide bonds to form insulin, and C-peptide. Binding of insulin to the insulin receptor (INSR) stimulates glucose uptake. A multitude of mutant alleles with phenotypic effects have been identified, including insulin-dependent diabetes mellitus, permanent neonatal diabetes diabetes mellitus, maturity-onset diabetes of the young type 10 and hyperproinsulinemia. There is a read-through gene, INS-IGF2, which overlaps with this gene at the 5' region and with the IGF2 gene at the 3' region. [provided by RefSeq, May 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.004797995).
BP6
?
Variant 11-2159843-G-A is Benign according to our data. Variant chr11-2159843-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INS | NM_000207.3 | c.*9C>T | 3_prime_UTR_variant | 3/3 | ENST00000381330.5 | ||
INS-IGF2 | NR_003512.4 | n.246+942C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INS | ENST00000381330.5 | c.*9C>T | 3_prime_UTR_variant | 3/3 | 1 | NM_000207.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.166 AC: 25164AN: 152042Hom.: 2320 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.173 AC: 42022AN: 243204Hom.: 4105 AF XY: 0.173 AC XY: 22829AN XY: 131994
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GnomAD4 exome AF: 0.204 AC: 296864AN: 1457624Hom.: 31767 Cov.: 37 AF XY: 0.202 AC XY: 146109AN XY: 724800
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GnomAD4 genome ? AF: 0.165 AC: 25162AN: 152160Hom.: 2322 Cov.: 33 AF XY: 0.160 AC XY: 11905AN XY: 74396
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 02, 2017 | - - |
Transient Neonatal Diabetes, Dominant/Recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Maturity onset diabetes mellitus in young Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 12610512, 14551916) - |
Autosomal recessive DOPA responsive dystonia Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Maturity-onset diabetes of the young type 10 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Hypoinsulinemia Other:1
association, no assertion criteria provided | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Mutations in this gene can cause early onset diabetes mellitus which is insulin dependent. Poor response to sulfonylureas, as this mutation can cause beta cell destruction. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P;P;P
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
D
ClinPred
T
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at