rs7166565

Positions:

• chr15-98946706-A-G
• chr15-98946706-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000875.5(IGF1R):​c.3588-1868A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,018 control chromosomes in the GnomAD database, including 19,863 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 0.50 (19863 hom., cov: 32)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1R	NM_000875.5	c.3588-1868A>G		intron_variant		ENST00000650285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1R	ENST00000650285.1	c.3588-1868A>G		intron_variant			NM_000875.5	P4
IGF1R	ENST00000649865.1	c.3585-1868A>G		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76370 AN: 151900 Hom.: 19838 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.503 AC: 76429 AN: 152018 Hom.: 19863 Cov.: 32 AF XY: 0.499 AC XY: 37101 AN XY: 74288

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.534

Alfa AF: 0.552 Hom.: 22421

Bravo AF: 0.495

Asia WGS AF: 0.440 AC: 1533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.26
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7166565; hg19: chr15-99489935;