rs4966036

Positions:

• chr15-98886520-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000875.5(IGF1R):​c.641-4805T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,104 control chromosomes in the GnomAD database, including 5,431 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 0.26 (5431 hom., cov: 32)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1R	NM_000875.5	c.641-4805T>C		intron_variant		ENST00000650285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1R	ENST00000650285.1	c.641-4805T>C		intron_variant			NM_000875.5	P4
	ENST00000558736.1	n.70-5668A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39226 AN: 151986 Hom.: 5416 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.258 AC: 39278 AN: 152104 Hom.: 5431 Cov.: 32 AF XY: 0.267 AC XY: 19834 AN XY: 74336

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.251

Alfa AF: 0.228 Hom.: 2188

Bravo AF: 0.257

Asia WGS AF: 0.282 AC: 980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.84
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs4966036; hg19: chr15-99429749;