rs11854132

Variant names:

• chr15-98686101-G-A
• rs11854132
• NM_000875.5:c.95-21461G>A

Variant summary

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

The NM_000875.5(IGF1R):​c.95-21461G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,094 control chromosomes in the GnomAD database, including 8,956 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 0.33 (8956 hom., cov: 32)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601
• Publications: 13 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.95-21461G>A		intron_variant	Intron 1 of 20	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.95-21461G>A		intron_variant	Intron 1 of 20		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000559925.5	n.95-21461G>A		intron_variant	Intron 1 of 9	1
IGF1R	ENST00000649865.1	c.95-21461G>A		intron_variant	Intron 1 of 20			ENSP00000496919.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49423 AN: 151976 Hom.: 8945 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.325 AC: 49477 AN: 152094 Hom.: 8956 Cov.: 32 AF XY: 0.320 AC XY: 23804 AN XY: 74352

African (AFR) AF: 0.488 AC: 20214 AN: 41454

American (AMR) AF: 0.315 AC: 4819 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 899 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1011 AN: 5168

South Asian (SAS) AF: 0.183 AC: 883 AN: 4818

European-Finnish (FIN) AF: 0.224 AC: 2367 AN: 10586

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18293 AN: 67994

Other (OTH) AF: 0.307 AC: 648 AN: 2110

Alfa AF: 0.286 Hom.: 21131

Bravo AF: 0.342

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.060
DANN	Benign	0.58
PhyloP100		-0.60
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: rs11854132; hg19: chr15-99229330;