15-98938603-C-T

Variant names:

• chr15-98938603-C-T
• rs2684799
• NM_000875.5:c.3298-598C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000875.5(IGF1R):​c.3298-598C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,986 control chromosomes in the GnomAD database, including 9,863 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 0.35 (9863 hom., cov: 33)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 10 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, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000875.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	NM_000875.5	MANE Select	c.3298-598C>T		intron	N/A	NP_000866.1	P08069
	IGF1R	NM_001291858.2		c.3295-598C>T		intron	N/A	NP_001278787.1	C9J5X1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	ENST00000650285.1	MANE Select	c.3298-598C>T		intron	N/A	ENSP00000497069.1	P08069
	IGF1R	ENST00000649865.1		c.3295-598C>T		intron	N/A	ENSP00000496919.1	C9J5X1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52507 AN: 151868 Hom.: 9859 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.360

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.345 AC: 52506 AN: 151986 Hom.: 9863 Cov.: 33 AF XY: 0.345 AC XY: 25659 AN XY: 74278

African (AFR) AF: 0.187 AC: 7730 AN: 41432

American (AMR) AF: 0.309 AC: 4716 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1499 AN: 3470

East Asian (EAS) AF: 0.322 AC: 1662 AN: 5160

South Asian (SAS) AF: 0.510 AC: 2454 AN: 4808

European-Finnish (FIN) AF: 0.402 AC: 4239 AN: 10534

Middle Eastern (MID) AF: 0.438 AC: 127 AN: 290

European-Non Finnish (NFE) AF: 0.427 AC: 29005 AN: 67992

Other (OTH) AF: 0.357 AC: 754 AN: 2114

Alfa AF: 0.403 Hom.: 49795

Bravo AF: 0.328

Asia WGS AF: 0.347 AC: 1208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.48
PhyloP100		0.17
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: rs2684799; hg19: chr15-99481832;