rs3743258

Positions:

• chr15-98899910-G-A

Variant summary

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

The NM_000875.5(IGF1R):​c.1247+289G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,982 control chromosomes in the GnomAD database, including 8,371 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 0.32 (8371 hom., cov: 32)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.1247+289G>A		intron_variant		ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.1247+289G>A		intron_variant			NM_000875.5	ENSP00000497069	P4
IGF1R	ENST00000559925.5	n.1247+289G>A		intron_variant, non_coding_transcript_variant		1
IGF1R	ENST00000558898.1	c.338+289G>A		intron_variant		5		ENSP00000454115
IGF1R	ENST00000649865.1	c.1247+289G>A		intron_variant				ENSP00000496919	A1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 48997 AN: 151864 Hom.: 8359 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.323 AC: 49061 AN: 151982 Hom.: 8371 Cov.: 32 AF XY: 0.332 AC XY: 24691 AN XY: 74278

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.327

Alfa AF: 0.319 Hom.: 1329

Bravo AF: 0.330

Asia WGS AF: 0.397 AC: 1378 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	1.7
DANN	Benign	0.64

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: rs3743258; hg19: chr15-99443139;