rs2684778

Variant names:

• chr15-98862610-C-T
• rs2684778
• NM_000875.5:c.641-28715C>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.641-28715C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,050 control chromosomes in the GnomAD database, including 3,817 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 (3817 hom., cov: 32)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.641-28715C>T		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.641-28715C>T		intron_variant	Intron 2 of 20		NM_000875.5	ENSP00000497069.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30179 AN: 151932 Hom.: 3813 Cov.: 32

Gnomad AFR AF: 0.0734

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.199 AC: 30194 AN: 152050 Hom.: 3817 Cov.: 32 AF XY: 0.208 AC XY: 15466 AN XY: 74280

African (AFR) AF: 0.0732 AC: 3038 AN: 41494

American (AMR) AF: 0.302 AC: 4604 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 669 AN: 3468

East Asian (EAS) AF: 0.423 AC: 2190 AN: 5176

South Asian (SAS) AF: 0.325 AC: 1566 AN: 4820

European-Finnish (FIN) AF: 0.302 AC: 3178 AN: 10528

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.209 AC: 14193 AN: 67982

Other (OTH) AF: 0.218 AC: 461 AN: 2110

Alfa AF: 0.202 Hom.: 443

Bravo AF: 0.191

Asia WGS AF: 0.276 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.13
DANN	Benign	0.41
PhyloP100		-1.3
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: rs2684778; hg19: chr15-99405839;