rs4966013

Variant names:

• chr15-98702155-G-A
• rs4966013
• NM_000875.5:c.95-5407G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-98702155-G-A
• chr15-98702155-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.95-5407G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 150,690 control chromosomes in the GnomAD database, including 30,960 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 0.64 (30960 hom., cov: 27)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• Publications: 11 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.686 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.95-5407G>A		intron	N/A	NP_000866.1	P08069
	IGF1R	NM_001291858.2		c.95-5407G>A		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.95-5407G>A		intron	N/A	ENSP00000497069.1	P08069
	IGF1R	ENST00000559925.5	TSL:1	n.95-5407G>A		intron	N/A
	IGF1R	ENST00000649865.1		c.95-5407G>A		intron	N/A	ENSP00000496919.1	C9J5X1

Frequencies

GnomAD3 genomes AF: 0.639 AC: 96213 AN: 150576 Hom.: 30936 Cov.: 27

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.639 AC: 96280 AN: 150690 Hom.: 30960 Cov.: 27 AF XY: 0.633 AC XY: 46534 AN XY: 73530

African (AFR) AF: 0.566 AC: 23156 AN: 40912

American (AMR) AF: 0.638 AC: 9655 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2366 AN: 3458

East Asian (EAS) AF: 0.533 AC: 2708 AN: 5078

South Asian (SAS) AF: 0.706 AC: 3356 AN: 4752

European-Finnish (FIN) AF: 0.599 AC: 6180 AN: 10310

Middle Eastern (MID) AF: 0.690 AC: 200 AN: 290

European-Non Finnish (NFE) AF: 0.691 AC: 46810 AN: 67770

Other (OTH) AF: 0.642 AC: 1341 AN: 2088

Alfa AF: 0.681 Hom.: 45061

Bravo AF: 0.631

Asia WGS AF: 0.651 AC: 2263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.74
PhyloP100		0.28
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: rs4966013; hg19: chr15-99245384;