15-98649525-CTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant names:

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

Variant summary

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

The NM_000875.5(IGF1R):​c.-51_-33dupTTTTTTTTTTTTTTTTTTT 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 0.00044 (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

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 = 0.000441 (55/124606) while in subpopulation NFE AF= 0.000644 (38/59012). AF 95% confidence interval is 0.000482. There are 0 homozygotes in gnomad4. There are 25 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.-51_-33dupTTTTTTTTTTTTTTTTTTT		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.-51_-33dupTTTTTTTTTTTTTTTTTTT		5_prime_UTR_variant	Exon 1 of 21		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000649865	c.-51_-33dupTTTTTTTTTTTTTTTTTTT		5_prime_UTR_variant	Exon 1 of 21			ENSP00000496919.1
IGF1R	ENST00000559925.5	n.-57_-56insTTTTTTTTTTTTTTTTTTT		upstream_gene_variant		1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000122

Gnomad4 ASJ exome AF: 0.000123

Gnomad4 EAS exome AF: 0.0000726

Gnomad4 SAS exome AF: 0.000306

Gnomad4 FIN exome AF: 0.0000824

Gnomad4 NFE exome AF: 0.0000602

Gnomad4 OTH exome AF: 0.0000688

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

Gnomad4 AFR AF: 0.000296

Gnomad4 AMR AF: 0.000317

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000249

Gnomad4 SAS AF: 0.000513

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000644

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;