chr15-98649525-C-CTTTTTT

Variant names:

• chr15-98649525-C-CTTTTTT
• rs544674838
• NM_000875.5:c.-38_-33dupTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000875.5(IGF1R):​c.-38_-33dupTTTTTT 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 0.00039 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00051 (2 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000393 (49/124628) while in subpopulation EAS AF= 0.00124 (5/4022). AF 95% confidence interval is 0.00049. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.-38_-33dupTTTTTT		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.-38_-33dupTTTTTT		5_prime_UTR_variant	Exon 1 of 21		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000649865	c.-38_-33dupTTTTTT		5_prime_UTR_variant	Exon 1 of 21			ENSP00000496919.1
IGF1R	ENST00000559925.5	n.-57_-56insTTTTTT		upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.000393 AC: 49 AN: 124628 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000890

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000159

Gnomad ASJ AF: 0.000330

Gnomad EAS AF: 0.00124

Gnomad SAS AF: 0.000765

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000593

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000505 AC: 304 AN: 601468 Hom.: 2 Cov.: 0 AF XY: 0.000486 AC XY: 156 AN XY: 320966

Gnomad4 AFR exome AF: 0.000216

Gnomad4 AMR exome AF: 0.000653

Gnomad4 ASJ exome AF: 0.000674

Gnomad4 EAS exome AF: 0.000145

Gnomad4 SAS exome AF: 0.00153

Gnomad4 FIN exome AF: 0.000357

Gnomad4 NFE exome AF: 0.000412

Gnomad4 OTH exome AF: 0.000379

GnomAD4 genome AF: 0.000393 AC: 49 AN: 124628 Hom.: 0 Cov.: 0 AF XY: 0.000336 AC XY: 20 AN XY: 59490

Gnomad4 AFR AF: 0.0000890

Gnomad4 AMR AF: 0.000159

Gnomad4 ASJ AF: 0.000330

Gnomad4 EAS AF: 0.00124

Gnomad4 SAS AF: 0.000765

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000593

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;