rs3784606

Variant names:

• chr15-98915252-A-G
• rs3784606
• NM_000875.5:c.1829-712A>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.1829-712A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,154 control chromosomes in the GnomAD database, including 3,625 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 0.21 (3625 hom., cov: 33)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.845
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.1829-712A>G		intron_variant	Intron 8 of 20	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.1829-712A>G		intron_variant	Intron 8 of 20		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000559925.5	n.1829-712A>G		intron_variant	Intron 8 of 9	1
IGF1R	ENST00000649865.1	c.1829-712A>G		intron_variant	Intron 8 of 20			ENSP00000496919.1
IGF1R	ENST00000560144.1	n.107-762A>G		intron_variant	Intron 1 of 3	3		ENSP00000456950.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31390 AN: 152036 Hom.: 3625 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.206 AC: 31408 AN: 152154 Hom.: 3625 Cov.: 33 AF XY: 0.212 AC XY: 15759 AN XY: 74380

African (AFR) AF: 0.101 AC: 4178 AN: 41540

American (AMR) AF: 0.216 AC: 3311 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3472

East Asian (EAS) AF: 0.212 AC: 1095 AN: 5168

South Asian (SAS) AF: 0.370 AC: 1783 AN: 4820

European-Finnish (FIN) AF: 0.303 AC: 3198 AN: 10562

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16349 AN: 67980

Other (OTH) AF: 0.228 AC: 482 AN: 2112

Alfa AF: 0.232 Hom.: 9630

Bravo AF: 0.193

Asia WGS AF: 0.255 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.16
DANN	Benign	0.46
PhyloP100		-0.84
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: rs3784606; hg19: chr15-99458481;