rs2229765
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000875.5(IGF1R):c.3129G>A(p.Glu1043=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,613,534 control chromosomes in the GnomAD database, including 151,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.39 ( 11963 hom., cov: 31)
Exomes 𝑓: 0.43 ( 139575 hom. )
Consequence
IGF1R
NM_000875.5 synonymous
NM_000875.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.148
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 15-98934996-G-A is Benign according to our data. Variant chr15-98934996-G-A is described in ClinVar as [Benign]. Clinvar id is 194610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-98934996-G-A is described in Lovd as [Likely_benign]. Variant chr15-98934996-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.148 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGF1R | NM_000875.5 | c.3129G>A | p.Glu1043= | synonymous_variant | 16/21 | ENST00000650285.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGF1R | ENST00000650285.1 | c.3129G>A | p.Glu1043= | synonymous_variant | 16/21 | NM_000875.5 | P4 | ||
IGF1R | ENST00000560972.1 | n.260-320G>A | intron_variant, non_coding_transcript_variant | 1 | |||||
IGF1R | ENST00000649865.1 | c.3126G>A | p.Glu1042= | synonymous_variant | 16/21 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.391 AC: 59377AN: 151908Hom.: 11959 Cov.: 31
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GnomAD3 exomes AF: 0.397 AC: 99711AN: 251348Hom.: 20615 AF XY: 0.398 AC XY: 54082AN XY: 135832
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GnomAD4 exome AF: 0.433 AC: 632746AN: 1461508Hom.: 139575 Cov.: 46 AF XY: 0.430 AC XY: 312426AN XY: 727054
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GnomAD4 genome ? AF: 0.391 AC: 59409AN: 152026Hom.: 11963 Cov.: 31 AF XY: 0.388 AC XY: 28824AN XY: 74304
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 17, 2014 | - - |
Growth delay due to insulin-like growth factor I resistance Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
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