rs2139924

chr15-98912041-C-Achr15-98912041-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IGF1R	NM_000875.5	c.1589+600C>A		intron_variant		ENST00000650285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1R	ENST00000650285.1	c.1589+600C>A		intron_variant			NM_000875.5	P4
IGF1R	ENST00000559925.5	n.1589+600C>A		intron_variant, non_coding_transcript_variant		1
IGF1R	ENST00000649865.1	c.1589+600C>A		intron_variant				A1
IGF1R	ENST00000559582.1	n.496+600C>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.808

Gnomad4 AMR AF: 0.709

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.804

Alfa AF: 0.817 Hom.: 30413

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2139924; hg19: chr15-99455270;