rs2293117

Variant names:

• chr15-98935484-T-C
• rs2293117
• NM_000875.5:c.3297+58T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 20 publications found

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]

IGF1R Gene-Disease associations (from GenCC):

• growth delay due to insulin-like growth factor I resistance

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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 rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.3297+58T>C		intron_variant	Intron 17 of 20	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.3297+58T>C		intron_variant	Intron 17 of 20		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000649865.1	c.3294+58T>C		intron_variant	Intron 17 of 20			ENSP00000496919.1
IGF1R	ENST00000560972.1	n.*118T>C		downstream_gene_variant		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

African (AFR) AF: 0.331 AC: 6836 AN: 20634

American (AMR) AF: 0.351 AC: 12306 AN: 35052

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 10264 AN: 21642

East Asian (EAS) AF: 0.305 AC: 10120 AN: 33158

South Asian (SAS) AF: 0.313 AC: 21232 AN: 67878

European-Finnish (FIN) AF: 0.426 AC: 20870 AN: 49038

Middle Eastern (MID) AF: 0.370 AC: 1717 AN: 4642

European-Non Finnish (NFE) AF: 0.457 AC: 254126 AN: 555496

Other (OTH) AF: 0.415 AC: 16321 AN: 39288

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

African (AFR) AF: 0.334 AC: 13832 AN: 41458

American (AMR) AF: 0.383 AC: 5855 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1615 AN: 3472

East Asian (EAS) AF: 0.340 AC: 1753 AN: 5162

South Asian (SAS) AF: 0.323 AC: 1553 AN: 4814

European-Finnish (FIN) AF: 0.419 AC: 4429 AN: 10576

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30843 AN: 67958

Other (OTH) AF: 0.385 AC: 810 AN: 2104

Alfa AF: 0.411 Hom.: 6601

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
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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