rs1319859

Variant names:

• chr15-98687034-G-A
• rs1319859
• NM_000875.5:c.95-20528G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

IGF1R Gene-Disease associations (from GenCC):

• growth delay due to insulin-like growth factor I resistance

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.95-20528G>A		intron_variant	Intron 1 of 20	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.95-20528G>A		intron_variant	Intron 1 of 20		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000559925.5	n.95-20528G>A		intron_variant	Intron 1 of 9	1
IGF1R	ENST00000649865.1	c.95-20528G>A		intron_variant	Intron 1 of 20			ENSP00000496919.1

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

African (AFR) AF: 0.246 AC: 10217 AN: 41458

American (AMR) AF: 0.608 AC: 9288 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2371 AN: 3470

East Asian (EAS) AF: 0.690 AC: 3558 AN: 5160

South Asian (SAS) AF: 0.682 AC: 3288 AN: 4822

European-Finnish (FIN) AF: 0.719 AC: 7585 AN: 10552

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46275 AN: 67978

Other (OTH) AF: 0.603 AC: 1274 AN: 2114

Alfa AF: 0.636 Hom.: 85294

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
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1319859; hg19: chr15-99230263;