rs2139924

Variant names:

• chr15-98912041-C-A
• rs2139924
• NM_000875.5:c.1589+600C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-98912041-C-A
• chr15-98912041-C-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.1589+600C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 151,958 control chromosomes in the GnomAD database, including 48,412 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 0.80 (48412 hom., cov: 31)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 8 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.1589+600C>A		intron_variant	Intron 7 of 20	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.1589+600C>A		intron_variant	Intron 7 of 20		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000559925.5	n.1589+600C>A		intron_variant	Intron 7 of 9	1
IGF1R	ENST00000649865.1	c.1589+600C>A		intron_variant	Intron 7 of 20			ENSP00000496919.1
IGF1R	ENST00000559582.1	n.496+600C>A		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.796 AC: 120813 AN: 151842 Hom.: 48396 Cov.: 31

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.804

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

GnomAD4 genome AF: 0.795 AC: 120877 AN: 151958 Hom.: 48412 Cov.: 31 AF XY: 0.790 AC XY: 58640 AN XY: 74248

African (AFR) AF: 0.808 AC: 33480 AN: 41424

American (AMR) AF: 0.709 AC: 10825 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 3176 AN: 3470

East Asian (EAS) AF: 0.570 AC: 2936 AN: 5150

South Asian (SAS) AF: 0.778 AC: 3743 AN: 4808

European-Finnish (FIN) AF: 0.779 AC: 8235 AN: 10566

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.820 AC: 55747 AN: 67948

Other (OTH) AF: 0.804 AC: 1699 AN: 2112

Alfa AF: 0.813 Hom.: 100315

Bravo AF: 0.791

Asia WGS AF: 0.695 AC: 2421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.057
DANN	Benign	0.61
PhyloP100		-1.4
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: rs2139924; hg19: chr15-99455270;