rs1521480

Variant names:

• chr15-98871174-G-A
• rs1521480
• NM_000875.5:c.641-20151G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-98871174-G-A
• chr15-98871174-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000875.5(IGF1R):​c.641-20151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,266 control chromosomes in the GnomAD database, including 3,617 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 0.19 (3617 hom., cov: 34)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.641-20151G>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.641-20151G>A		intron_variant	Intron 2 of 20		NM_000875.5	ENSP00000497069.1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28722 AN: 152150 Hom.: 3617 Cov.: 34

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.189 AC: 28732 AN: 152266 Hom.: 3617 Cov.: 34 AF XY: 0.200 AC XY: 14854 AN XY: 74444

African (AFR) AF: 0.0443 AC: 1840 AN: 41570

American (AMR) AF: 0.287 AC: 4398 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3472

East Asian (EAS) AF: 0.405 AC: 2098 AN: 5178

South Asian (SAS) AF: 0.289 AC: 1394 AN: 4828

European-Finnish (FIN) AF: 0.323 AC: 3417 AN: 10588

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14413 AN: 68012

Other (OTH) AF: 0.201 AC: 424 AN: 2114

Alfa AF: 0.177 Hom.: 1168

Bravo AF: 0.178

Asia WGS AF: 0.256 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.77
DANN	Benign	0.50
PhyloP100		-0.19
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: rs1521480; hg19: chr15-99414403;