15-98910334-A-G

Variant names:

• chr15-98910334-A-G
• rs2684811
• NM_000875.5:c.1463-981A>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.1463-981A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,150 control chromosomes in the GnomAD database, including 37,100 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 0.69 (37100 hom., cov: 34)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 18 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.1463-981A>G		intron_variant	Intron 6 of 20	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.1463-981A>G		intron_variant	Intron 6 of 20		NM_000875.5	ENSP00000497069.1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104774 AN: 152032 Hom.: 37075 Cov.: 34

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.689 AC: 104846 AN: 152150 Hom.: 37100 Cov.: 34 AF XY: 0.678 AC XY: 50402 AN XY: 74388

African (AFR) AF: 0.594 AC: 24622 AN: 41478

American (AMR) AF: 0.624 AC: 9540 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3011 AN: 3470

East Asian (EAS) AF: 0.405 AC: 2099 AN: 5186

South Asian (SAS) AF: 0.613 AC: 2950 AN: 4816

European-Finnish (FIN) AF: 0.675 AC: 7158 AN: 10600

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53118 AN: 68002

Other (OTH) AF: 0.707 AC: 1488 AN: 2106

Alfa AF: 0.743 Hom.: 90579

Bravo AF: 0.681

Asia WGS AF: 0.581 AC: 2024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.27
PhyloP100		-0.10
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: rs2684811; hg19: chr15-99453563; COSMIC: COSV51398048; COSMIC: COSV51398048;