chr15-98649525-CTTTTTTTTTT-C

Variant names:

• chr15-98649525-CTTTTTTTTTT-C
• rs544674838
• NM_000875.5:c.-42_-33delTTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000875.5(IGF1R):​c.-42_-33delTTTTTTTTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 581,986 control chromosomes in the GnomAD database, including 136 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00043 (1 hom., cov: 0)
  • Exomes 𝑓: 0.050 (136 hom.)
  • Failed GnomAD Quality Control
• Consequence: IGF1R NM_000875.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.-42_-33delTTTTTTTTTT		5_prime_UTR_variant	Exon 1 of 21	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285	c.-42_-33delTTTTTTTTTT		5_prime_UTR_variant	Exon 1 of 21		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000649865	c.-42_-33delTTTTTTTTTT		5_prime_UTR_variant	Exon 1 of 21			ENSP00000496919.1
IGF1R	ENST00000559925.5	n.-56_-47delTTTTTTTTTT		upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 53 AN: 124642 Hom.: 1 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.000148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000794

Gnomad ASJ AF: 0.000329

Gnomad EAS AF: 0.000746

Gnomad SAS AF: 0.00128

Gnomad FIN AF: 0.000889

Gnomad MID AF: 0.00870

Gnomad NFE AF: 0.000508

Gnomad OTH AF: 0.000598

GnomAD4 exome AF: 0.0505 AC: 29381 AN: 581986 Hom.: 136 AF XY: 0.0487 AC XY: 15102 AN XY: 310288

Gnomad4 AFR exome AF: 0.0176

Gnomad4 AMR exome AF: 0.0393

Gnomad4 ASJ exome AF: 0.0303

Gnomad4 EAS exome AF: 0.0409

Gnomad4 SAS exome AF: 0.0353

Gnomad4 FIN exome AF: 0.0547

Gnomad4 NFE exome AF: 0.0560

Gnomad4 OTH exome AF: 0.0433

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000425 AC: 53 AN: 124650 Hom.: 1 Cov.: 0 AF XY: 0.000403 AC XY: 24 AN XY: 59516

Gnomad4 AFR AF: 0.000148

Gnomad4 AMR AF: 0.0000793

Gnomad4 ASJ AF: 0.000329

Gnomad4 EAS AF: 0.000748

Gnomad4 SAS AF: 0.00128

Gnomad4 FIN AF: 0.000889

Gnomad4 NFE AF: 0.000508

Gnomad4 OTH AF: 0.000594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs544674838; hg19: chr15-99192754;