15-98791393-A-T

Variant names:

• chr15-98791393-A-T
• rs2871975
• NM_000875.5:c.640+83286A>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.640+83286A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,222 control chromosomes in the GnomAD database, including 57,109 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 0.85 (57109 hom., cov: 33)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 0 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 (NFE) allele frequency at 95% confidence interval = 0.967 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.640+83286A>T		intron	N/A	NP_000866.1	P08069
	IGF1R	NM_001291858.2		c.640+83286A>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.640+83286A>T		intron	N/A	ENSP00000497069.1	P08069
	IGF1R	ENST00000559925.5	TSL:1	n.640+83286A>T		intron	N/A
	IGF1R	ENST00000649865.1		c.640+83286A>T		intron	N/A	ENSP00000496919.1	C9J5X1

Frequencies

GnomAD3 genomes AF: 0.848 AC: 129033 AN: 152104 Hom.: 57109 Cov.: 33

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.933

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.974

Gnomad OTH AF: 0.879

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

GnomAD4 genome AF: 0.848 AC: 129056 AN: 152222 Hom.: 57109 Cov.: 33 AF XY: 0.848 AC XY: 63151 AN XY: 74446

African (AFR) AF: 0.568 AC: 23566 AN: 41470

American (AMR) AF: 0.893 AC: 13654 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 3387 AN: 3472

East Asian (EAS) AF: 0.857 AC: 4440 AN: 5180

South Asian (SAS) AF: 0.932 AC: 4505 AN: 4832

European-Finnish (FIN) AF: 0.963 AC: 10222 AN: 10614

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.974 AC: 66235 AN: 68034

Other (OTH) AF: 0.879 AC: 1860 AN: 2116

Alfa AF: 0.846 Hom.: 2173

Bravo AF: 0.829

Asia WGS AF: 0.879 AC: 3049 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.27
DANN	Benign	0.68
PhyloP100		-1.2
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: rs2871975; hg19: chr15-99334622;