rs3842740
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1
The NM_000207.3(INS):c.-18+4_-18+5insTTGC variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 737,138 control chromosomes in the GnomAD database, including 1,550 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.068 ( 1118 hom., cov: 34)
Exomes 𝑓: 0.0083 ( 432 hom. )
Consequence
INS
NM_000207.3 splice_donor_region, intron
NM_000207.3 splice_donor_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.23
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 -9 ACMG points.
BP6
?
Variant 11-2161163-C-CGCAA is Benign according to our data. Variant chr11-2161163-C-CGCAA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 304060.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Likely_benign=2, Uncertain_significance=1}.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INS | NM_000207.3 | c.-18+4_-18+5insTTGC | splice_donor_region_variant, intron_variant | ENST00000381330.5 | |||
INS-IGF2 | NR_003512.4 | n.42+4_42+5insTTGC | splice_donor_region_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INS | ENST00000250971.7 | c.-40_-39insTTGC | 5_prime_UTR_variant | 1/3 | 1 | P1 | |||
INS | ENST00000397262.5 | c.-193_-192insTTGC | 5_prime_UTR_variant | 1/2 | 1 | P1 | |||
INS | ENST00000381330.5 | c.-18+4_-18+5insTTGC | splice_donor_region_variant, intron_variant | 1 | NM_000207.3 | P1 | |||
INS | ENST00000421783.1 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0675 AC: 10275AN: 152134Hom.: 1112 Cov.: 34
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GnomAD4 exome AF: 0.00828 AC: 4844AN: 584886Hom.: 432 Cov.: 7 AF XY: 0.00727 AC XY: 2185AN XY: 300438
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GnomAD4 genome ? AF: 0.0676 AC: 10297AN: 152252Hom.: 1118 Cov.: 34 AF XY: 0.0657 AC XY: 4891AN XY: 74454
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Maturity-onset diabetes of the young type 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Potent mutations in INS gene can cause early onset diabetes mellitus which is insulin dependent. May have poor response to sulfonylureas, as mutations in this gene can cause beta cell destruction. However no sufficient evidence is found to ascertain the role of this particular variant rs3842740, yet. - |
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 | Sep 04, 2018 | This variant is associated with the following publications: (PMID: 16380501, 20628762, 19247282) - |
Autosomal recessive DOPA responsive dystonia Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at