rs891088
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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.653-114T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 777,212 control chromosomes in the GnomAD database, including 34,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.32 ( 8511 hom., cov: 32)
Exomes 𝑓: 0.27 ( 26393 hom. )
Consequence
INSR
NM_000208.4 intron
NM_000208.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.725
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=-0.87).
BP6
?
Variant 19-7184751-A-G is Benign according to our data. Variant chr19-7184751-A-G is described in ClinVar as [Benign]. Clinvar id is 1286680.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INSR | NM_000208.4 | c.653-114T>C | intron_variant | ENST00000302850.10 | |||
INSR | NM_001079817.3 | c.653-114T>C | intron_variant | ||||
INSR | XM_011527988.3 | c.653-114T>C | intron_variant | ||||
INSR | XM_011527989.4 | c.653-114T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INSR | ENST00000302850.10 | c.653-114T>C | intron_variant | 1 | NM_000208.4 | A2 | |||
INSR | ENST00000341500.9 | c.653-114T>C | intron_variant | 1 | P3 | ||||
INSR | ENST00000598216.1 | n.628-114T>C | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.321 AC: 48828AN: 151888Hom.: 8479 Cov.: 32
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GnomAD4 exome AF: 0.271 AC: 169620AN: 625206Hom.: 26393 AF XY: 0.273 AC XY: 86678AN XY: 317048
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GnomAD4 genome ? AF: 0.322 AC: 48908AN: 152006Hom.: 8511 Cov.: 32 AF XY: 0.324 AC XY: 24075AN XY: 74306
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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 | Nov 12, 2018 | - - |
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