chr15-98649689-C-T
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_000875.5(IGF1R):c.94+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,593,810 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0097 ( 20 hom., cov: 32)
Exomes 𝑓: 0.00088 ( 11 hom. )
Consequence
IGF1R
NM_000875.5 intron
NM_000875.5 intron
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 0.681
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 -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
Variant 15-98649689-C-T is Benign according to our data. Variant chr15-98649689-C-T is described in ClinVar as [Benign]. Clinvar id is 317439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-98649689-C-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00968 (1473/152142) while in subpopulation AFR AF= 0.0337 (1399/41536). AF 95% confidence interval is 0.0322. There are 20 homozygotes in gnomad4. There are 723 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 20 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGF1R | NM_000875.5 | c.94+14C>T | intron_variant | ENST00000650285.1 | |||
IRAIN | NR_126453.2 | n.1099G>A | non_coding_transcript_exon_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGF1R | ENST00000650285.1 | c.94+14C>T | intron_variant | NM_000875.5 | P4 | ||||
IGF1R | ENST00000559925.5 | n.94+14C>T | intron_variant, non_coding_transcript_variant | 1 | |||||
IGF1R | ENST00000649865.1 | c.94+14C>T | intron_variant | A1 |
Frequencies
GnomAD3 genomes AF: 0.00967 AC: 1470AN: 152036Hom.: 20 Cov.: 32
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GnomAD3 exomes AF: 0.00231 AC: 568AN: 245420Hom.: 10 AF XY: 0.00187 AC XY: 249AN XY: 133496
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GnomAD4 exome AF: 0.000875 AC: 1262AN: 1441668Hom.: 11 Cov.: 28 AF XY: 0.000777 AC XY: 558AN XY: 718222
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GnomAD4 genome AF: 0.00968 AC: 1473AN: 152142Hom.: 20 Cov.: 32 AF XY: 0.00972 AC XY: 723AN XY: 74374
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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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