rs2871865

Variant names:

• chr15-98651667-C-G
• rs2871865
• NM_000875.5:c.94+1992C>G

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+1992C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,118 control chromosomes in the GnomAD database, including 4,706 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 0.20 (4706 hom., cov: 33)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 57 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

ENSG00000278022 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.94+1992C>G		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+1992C>G		intron_variant	Intron 1 of 20		NM_000875.5	ENSP00000497069.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30476 AN: 152000 Hom.: 4677 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0555

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.201 AC: 30559 AN: 152118 Hom.: 4706 Cov.: 33 AF XY: 0.196 AC XY: 14593 AN XY: 74368

African (AFR) AF: 0.431 AC: 17854 AN: 41456

American (AMR) AF: 0.154 AC: 2360 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 581 AN: 3468

East Asian (EAS) AF: 0.107 AC: 554 AN: 5160

South Asian (SAS) AF: 0.148 AC: 716 AN: 4830

European-Finnish (FIN) AF: 0.0555 AC: 588 AN: 10598

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.109 AC: 7412 AN: 68000

Other (OTH) AF: 0.176 AC: 371 AN: 2110

Alfa AF: 0.154 Hom.: 373

Bravo AF: 0.219

Asia WGS AF: 0.145 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.40
PhyloP100		-0.084
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: rs2871865; hg19: chr15-99194896;