rs2141155132

Variant names:

• chr15-98649621-TG-T
• rs2141155132
• NM_000875.5:c.45delG

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000875.5(IGF1R):​c.45delG​(p.Leu16SerfsTer31) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IGF1R NM_000875.5 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.69
• Publications: 1 publications found

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]

IRAIN (HGNC:50365): (IGF1R antisense imprinted non-protein coding RNA) This gene expresses a long non-coding RNA in antisense to the insulin-like growth factor type I receptor (IGF1R) gene. This transcript is imprinted and expressed from the paternal allele. It interacts with chromatin and may promote long-range DNA interactions that influence the regulation of gene expression. [provided by RefSeq, Nov 2015]

ENSG00000278022 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 61 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-98649621-TG-T is Pathogenic according to our data. Variant chr15-98649621-TG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 2875102.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000875.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	NM_000875.5	MANE Select	c.45delG	p.Leu16SerfsTer31	frameshift	Exon 1 of 21	NP_000866.1	P08069
	IGF1R	NM_001291858.2		c.45delG	p.Leu16SerfsTer31	frameshift	Exon 1 of 21	NP_001278787.1	C9J5X1
	IRAIN	NR_126453.2		n.1166delC		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	ENST00000650285.1	MANE Select	c.45delG	p.Leu16SerfsTer31	frameshift	Exon 1 of 21	ENSP00000497069.1	P08069
	IGF1R	ENST00000559925.5	TSL:1	n.45delG		non_coding_transcript_exon	Exon 1 of 10
	IGF1R	ENST00000649865.1		c.45delG	p.Leu16SerfsTer31	frameshift	Exon 1 of 21	ENSP00000496919.1	C9J5X1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2141155132; hg19: chr15-99192850;