rs2252673
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000208.4(INSR):c.2267+90G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,251,622 control chromosomes in the GnomAD database, including 392,313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.74 ( 42976 hom., cov: 34)
Exomes 𝑓: 0.79 ( 349337 hom. )
Consequence
INSR
NM_000208.4 intron
NM_000208.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.462
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 19-7150407-C-G is Benign according to our data. Variant chr19-7150407-C-G is described in ClinVar as [Benign]. Clinvar id is 1246658.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INSR | NM_000208.4 | c.2267+90G>C | intron_variant | ENST00000302850.10 | |||
INSR | NM_001079817.3 | c.2231+2319G>C | intron_variant | ||||
INSR | XM_011527988.3 | c.2267+90G>C | intron_variant | ||||
INSR | XM_011527989.4 | c.2231+2319G>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INSR | ENST00000302850.10 | c.2267+90G>C | intron_variant | 1 | NM_000208.4 | A2 | |||
INSR | ENST00000341500.9 | c.2231+2319G>C | intron_variant | 1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.744 AC: 113081AN: 152056Hom.: 42953 Cov.: 34
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GnomAD4 exome AF: 0.789 AC: 867898AN: 1099446Hom.: 349337 AF XY: 0.791 AC XY: 443326AN XY: 560728
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GnomAD4 genome ? AF: 0.744 AC: 113143AN: 152176Hom.: 42976 Cov.: 34 AF XY: 0.736 AC XY: 54743AN XY: 74372
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at