rs1058696
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1
The NM_000875.5(IGF1R):c.*1856C>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 0.05 in 233,598 control chromosomes in the GnomAD database, including 374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.052 ( 264 hom., cov: 33)
Exomes 𝑓: 0.045 ( 110 hom. )
Consequence
IGF1R
NM_000875.5 3_prime_UTR
NM_000875.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.24
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 15-98959298-C-T is Benign according to our data. Variant chr15-98959298-C-T is described in ClinVar as [Benign]. Clinvar id is 317517.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0775 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGF1R | NM_000875.5 | c.*1856C>T | 3_prime_UTR_variant | 21/21 | ENST00000650285.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGF1R | ENST00000650285.1 | c.*1856C>T | 3_prime_UTR_variant | 21/21 | NM_000875.5 | P4 | |||
SYNM-AS1 | ENST00000559468.1 | n.349-4910G>A | intron_variant, non_coding_transcript_variant | 4 | |||||
IGF1R | ENST00000649865.1 | c.*1856C>T | 3_prime_UTR_variant | 21/21 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0524 AC: 7975AN: 152222Hom.: 263 Cov.: 33
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GnomAD4 exome AF: 0.0454 AC: 3693AN: 81258Hom.: 110 Cov.: 0 AF XY: 0.0445 AC XY: 1665AN XY: 37422
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GnomAD4 genome ? AF: 0.0524 AC: 7981AN: 152340Hom.: 264 Cov.: 33 AF XY: 0.0526 AC XY: 3918AN XY: 74502
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Growth delay due to insulin-like growth factor I resistance Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
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