NM_000875.5:c.-51_-33dupTTTTTTTTTTTTTTTTTTT

Variant names:

• chr15-98649525-C-CTTTTTTTTTTTTTTTTTTT
• rs544674838
• NM_000875.5:c.-51_-33dupTTTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000875.5(IGF1R):​c.-51_-33dupTTTTTTTTTTTTTTTTTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000086 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: IGF1R NM_000875.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

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.-51_-33dupTTTTTTTTTTTTTTTTTTT		5_prime_UTR	Exon 1 of 21	NP_000866.1	P08069
	IGF1R	NM_001291858.2		c.-51_-33dupTTTTTTTTTTTTTTTTTTT		5_prime_UTR	Exon 1 of 21	NP_001278787.1	C9J5X1
	IRAIN	NR_126453.2		n.1244_1262dupAAAAAAAAAAAAAAAAAAA		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.-51_-33dupTTTTTTTTTTTTTTTTTTT		5_prime_UTR	Exon 1 of 21	ENSP00000497069.1	P08069
	IGF1R	ENST00000649865.1		c.-51_-33dupTTTTTTTTTTTTTTTTTTT		5_prime_UTR	Exon 1 of 21	ENSP00000496919.1	C9J5X1
	ENSG00000278022	ENST00000747447.1		n.83+2300_83+2318dupTTTTTTTTTTTTTTTTTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000441 AC: 55 AN: 124598 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000318

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000249

Gnomad SAS AF: 0.000510

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000644

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000864 AC: 52 AN: 601542 Hom.: 2 Cov.: 0 AF XY: 0.0000997 AC XY: 32 AN XY: 321008

African (AFR) AF: 0.00 AC: 0 AN: 13902

American (AMR) AF: 0.000122 AC: 3 AN: 24498

Ashkenazi Jewish (ASJ) AF: 0.000123 AC: 2 AN: 16324

East Asian (EAS) AF: 0.0000726 AC: 2 AN: 27560

South Asian (SAS) AF: 0.000306 AC: 16 AN: 52282

European-Finnish (FIN) AF: 0.0000824 AC: 3 AN: 36386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2964

European-Non Finnish (NFE) AF: 0.0000602 AC: 24 AN: 398562

Other (OTH) AF: 0.0000688 AC: 2 AN: 29064

GnomAD4 genome AF: 0.000441 AC: 55 AN: 124606 Hom.: 0 Cov.: 0 AF XY: 0.000420 AC XY: 25 AN XY: 59498

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000296 AC: 10 AN: 33738

American (AMR) AF: 0.000317 AC: 4 AN: 12600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3036

East Asian (EAS) AF: 0.000249 AC: 1 AN: 4010

South Asian (SAS) AF: 0.000513 AC: 2 AN: 3896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.000644 AC: 38 AN: 59012

Other (OTH) AF: 0.00 AC: 0 AN: 1682

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.29

Splicing

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

Other links and lift over

dbSNP: rs544674838; hg19: chr15-99192754;