15-98667602-C-T

Variant names:

• chr15-98667602-C-T
• rs11247362
• NM_000875.5:c.94+17927C>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.94+17927C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 151,984 control chromosomes in the GnomAD database, including 46,585 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 0.75 (46585 hom., cov: 31)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.667
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.94+17927C>T		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.94+17927C>T		intron_variant	Intron 1 of 20		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000559925.5	n.94+17927C>T		intron_variant	Intron 1 of 9	1
IGF1R	ENST00000649865.1	c.94+17927C>T		intron_variant	Intron 1 of 20			ENSP00000496919.1

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113282 AN: 151866 Hom.: 46577 Cov.: 31

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.746 AC: 113323 AN: 151984 Hom.: 46585 Cov.: 31 AF XY: 0.751 AC XY: 55796 AN XY: 74304

African (AFR) AF: 0.365 AC: 15078 AN: 41352

American (AMR) AF: 0.827 AC: 12634 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.854 AC: 2963 AN: 3470

East Asian (EAS) AF: 0.892 AC: 4563 AN: 5114

South Asian (SAS) AF: 0.833 AC: 4017 AN: 4822

European-Finnish (FIN) AF: 0.946 AC: 10046 AN: 10618

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.901 AC: 61281 AN: 68016

Other (OTH) AF: 0.787 AC: 1663 AN: 2114

Alfa AF: 0.817 Hom.: 9091

Bravo AF: 0.719

Asia WGS AF: 0.826 AC: 2871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.67
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11247362; hg19: chr15-99210831;