rs2293117

Positions:

• chr15-98935484-T-C
• chr15-98935484-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000875.5(IGF1R):​c.3297+58T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 978,858 control chromosomes in the GnomAD database, including 90,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.40 (12561 hom., cov: 31)
  • Exomes 𝑓: 0.43 (77456 hom.)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-98935484-T-C is Benign according to our data. Variant chr15-98935484-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.3297+58T>C		intron_variant		ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.3297+58T>C		intron_variant			NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000649865.1	c.3294+58T>C		intron_variant				ENSP00000496919.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61173 AN: 151912 Hom.: 12550 Cov.: 31

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.428 AC: 353792 AN: 826828 Hom.: 77456 AF XY: 0.424 AC XY: 182177 AN XY: 429796

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.351

Gnomad4 ASJ exome AF: 0.474

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.457

Gnomad4 OTH exome AF: 0.415

GnomAD4 genome AF: 0.403 AC: 61216 AN: 152030 Hom.: 12561 Cov.: 31 AF XY: 0.400 AC XY: 29710 AN XY: 74320

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.385

Alfa AF: 0.408 Hom.: 5792

Bravo AF: 0.398

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2293117; hg19: chr15-99478713; COSMIC: COSV51297004; COSMIC: COSV51297004;