rs8039666

Variant names:

• chr15-98908149-A-C
• rs8039666
• NM_000875.5:c.1248-536A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-98908149-A-C
• chr15-98908149-A-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.1248-536A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,202 control chromosomes in the GnomAD database, including 1,916 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 0.15 (1916 hom., cov: 33)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.750
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 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.1248-536A>C		intron	N/A	NP_000866.1	P08069
	IGF1R	NM_001291858.2		c.1248-536A>C		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.1248-536A>C		intron	N/A	ENSP00000497069.1	P08069
	IGF1R	ENST00000559925.5	TSL:1	n.1248-536A>C		intron	N/A
	IGF1R	ENST00000649865.1		c.1248-536A>C		intron	N/A	ENSP00000496919.1	C9J5X1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23213 AN: 152084 Hom.: 1909 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.153 AC: 23241 AN: 152202 Hom.: 1916 Cov.: 33 AF XY: 0.153 AC XY: 11359 AN XY: 74422

African (AFR) AF: 0.196 AC: 8143 AN: 41534

American (AMR) AF: 0.149 AC: 2277 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3470

East Asian (EAS) AF: 0.146 AC: 753 AN: 5168

South Asian (SAS) AF: 0.119 AC: 575 AN: 4828

European-Finnish (FIN) AF: 0.128 AC: 1355 AN: 10598

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9342 AN: 67992

Other (OTH) AF: 0.155 AC: 326 AN: 2110

Alfa AF: 0.0782 Hom.: 99

Bravo AF: 0.157

Asia WGS AF: 0.156 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.78
PhyloP100		0.75
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: rs8039666; hg19: chr15-99451378;