rs907806

Variant names:

• chr15-98801652-G-A
• rs907806
• NM_000875.5:c.641-89673G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-98801652-G-A
• chr15-98801652-G-C
• chr15-98801652-G-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.641-89673G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,260 control chromosomes in the GnomAD database, including 53,913 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 0.84 (53913 hom., cov: 34)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• 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 = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.641-89673G>A		intron_variant	Intron 2 of 20	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.641-89673G>A		intron_variant	Intron 2 of 20		NM_000875.5	ENSP00000497069.1

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127648 AN: 152142 Hom.: 53883 Cov.: 34

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.882

Gnomad OTH AF: 0.827

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

GnomAD4 genome AF: 0.839 AC: 127724 AN: 152260 Hom.: 53913 Cov.: 34 AF XY: 0.837 AC XY: 62294 AN XY: 74450

African (AFR) AF: 0.746 AC: 30965 AN: 41518

American (AMR) AF: 0.846 AC: 12949 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2927 AN: 3472

East Asian (EAS) AF: 0.854 AC: 4418 AN: 5174

South Asian (SAS) AF: 0.830 AC: 4009 AN: 4832

European-Finnish (FIN) AF: 0.910 AC: 9654 AN: 10614

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.882 AC: 60024 AN: 68034

Other (OTH) AF: 0.827 AC: 1744 AN: 2108

Alfa AF: 0.844 Hom.: 4683

Bravo AF: 0.831

Asia WGS AF: 0.837 AC: 2909 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	0.059
DANN	Benign	0.69
PhyloP100		-1.9
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: rs907806; hg19: chr15-99344881;