rs1319859

Positions:

• chr15-98687034-G-A
• chr15-98687034-G-T

Variant summary

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

The NM_000875.5(IGF1R):​c.95-20528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,028 control chromosomes in the GnomAD database, including 26,477 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 0.56 (26477 hom., cov: 32)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.95-20528G>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.95-20528G>A		intron_variant			NM_000875.5	ENSP00000497069	P4
IGF1R	ENST00000559925.5	n.95-20528G>A		intron_variant, non_coding_transcript_variant		1
IGF1R	ENST00000649865.1	c.95-20528G>A		intron_variant				ENSP00000496919	A1

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84683 AN: 151910 Hom.: 26475 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.557 AC: 84697 AN: 152028 Hom.: 26477 Cov.: 32 AF XY: 0.562 AC XY: 41765 AN XY: 74286

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.603

Alfa AF: 0.664 Hom.: 54245

Bravo AF: 0.533

Asia WGS AF: 0.653 AC: 2269 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	1.3
DANN	Benign	0.56

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: rs1319859; hg19: chr15-99230263;