rs1357112

Positions:

• chr15-98890147-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.641-1178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,090 control chromosomes in the GnomAD database, including 34,562 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 0.67 (34562 hom., cov: 32)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1R	NM_000875.5	c.641-1178G>A		intron_variant		ENST00000650285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1R	ENST00000650285.1	c.641-1178G>A		intron_variant			NM_000875.5	P4
	ENST00000558736.1	n.69+3320C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101747 AN: 151972 Hom.: 34509 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.670 AC: 101856 AN: 152090 Hom.: 34562 Cov.: 32 AF XY: 0.678 AC XY: 50402 AN XY: 74326

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.816

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.692

Alfa AF: 0.653 Hom.: 27738

Bravo AF: 0.672

Asia WGS AF: 0.873 AC: 3032 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	0.99
DANN	Benign	0.55

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: rs1357112; hg19: chr15-99433376; COSMIC: COSV51305618; COSMIC: COSV51305618;