rs2272037
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000875.5(IGF1R):c.1590-20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,587,368 control chromosomes in the GnomAD database, including 275,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..
Frequency
Genomes: 𝑓 0.50 ( 21247 hom., cov: 33)
Exomes 𝑓: 0.59 ( 254272 hom. )
Consequence
IGF1R
NM_000875.5 intron
NM_000875.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.26
Genes affected
IGF1R (HGNC:5465): (insulin like growth factor 1 receptor) This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The insulin-like growth factor I receptor plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
This place is a probable branch point but rather VUS (scored 4 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 15-98913024-T-C is Benign according to our data. Variant chr15-98913024-T-C is described in ClinVar as [Benign]. Clinvar id is 284932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-98913024-T-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IGF1R | NM_000875.5 | c.1590-20T>C | intron_variant | ENST00000650285.1 | NP_000866.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IGF1R | ENST00000650285.1 | c.1590-20T>C | intron_variant | NM_000875.5 | ENSP00000497069 | P4 | ||||
IGF1R | ENST00000559925.5 | n.1590-20T>C | intron_variant, non_coding_transcript_variant | 1 | ||||||
IGF1R | ENST00000649865.1 | c.1590-20T>C | intron_variant | ENSP00000496919 | A1 | |||||
IGF1R | ENST00000559582.1 | n.497-20T>C | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.503 AC: 76419AN: 152038Hom.: 21244 Cov.: 33
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GnomAD3 exomes AF: 0.584 AC: 146341AN: 250460Hom.: 44006 AF XY: 0.588 AC XY: 79658AN XY: 135468
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GnomAD4 exome AF: 0.592 AC: 849343AN: 1435212Hom.: 254272 Cov.: 26 AF XY: 0.593 AC XY: 424182AN XY: 715682
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GnomAD4 genome AF: 0.503 AC: 76462AN: 152156Hom.: 21247 Cov.: 33 AF XY: 0.509 AC XY: 37839AN XY: 74370
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 17, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
BranchPoint Hunter
RBP_binding_hub_radar
RBP_regulation_power_radar
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