chr15-98649525-C-CTTTTTTTTTT

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_000875.5(IGF1R):​c.-42_-33dupTTTTTTTTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: IGF1R NM_000875.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000634 (79/124592) while in subpopulation NFE AF= 0.000864 (51/59018). AF 95% confidence interval is 0.000674. There are 0 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.-42_-33dupTTTTTTTTTT		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_-33dupTTTTTTTTTT		5_prime_UTR_variant	Exon 1 of 21		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000649865	c.-42_-33dupTTTTTTTTTT		5_prime_UTR_variant	Exon 1 of 21			ENSP00000496919.1
IGF1R	ENST00000559925.5	n.-57_-56insTTTTTTTTTT		upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.000634 AC: 79 AN: 124592 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000148

Gnomad AMI AF: 0.00756

Gnomad AMR AF: 0.000794

Gnomad ASJ AF: 0.000989

Gnomad EAS AF: 0.000746

Gnomad SAS AF: 0.000255

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000864

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000216 AC: 130 AN: 601532 Hom.: 0 Cov.: 0 AF XY: 0.000227 AC XY: 73 AN XY: 321002

Gnomad4 AFR exome AF: 0.0000719

Gnomad4 AMR exome AF: 0.000122

Gnomad4 ASJ exome AF: 0.000245

Gnomad4 EAS exome AF: 0.000218

Gnomad4 SAS exome AF: 0.000650

Gnomad4 FIN exome AF: 0.000192

Gnomad4 NFE exome AF: 0.000176

Gnomad4 OTH exome AF: 0.000172

GnomAD4 genome AF: 0.000634 AC: 79 AN: 124592 Hom.: 0 Cov.: 0 AF XY: 0.000471 AC XY: 28 AN XY: 59476

Gnomad4 AFR AF: 0.000148

Gnomad4 AMR AF: 0.000794

Gnomad4 ASJ AF: 0.000989

Gnomad4 EAS AF: 0.000746

Gnomad4 SAS AF: 0.000255

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000864

Gnomad4 OTH AF: 0.00

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;