NM_000875.5:c.3587+814A>G

Variant names:

• chr15-98943866-A-G
• rs1568502
• NM_000875.5:c.3587+814A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000875.5(IGF1R):​c.3587+814A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,212 control chromosomes in the GnomAD database, including 3,171 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 0.19 (3171 hom., cov: 33)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 4 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=-0.61).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.3587+814A>G		intron_variant	Intron 19 of 20	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.3587+814A>G		intron_variant	Intron 19 of 20		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000649865.1	c.3584+814A>G		intron_variant	Intron 19 of 20			ENSP00000496919.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28912 AN: 152094 Hom.: 3171 Cov.: 33

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.190 AC: 28908 AN: 152212 Hom.: 3171 Cov.: 33 AF XY: 0.193 AC XY: 14343 AN XY: 74424

African (AFR) AF: 0.0760 AC: 3157 AN: 41536

American (AMR) AF: 0.179 AC: 2746 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 875 AN: 3468

East Asian (EAS) AF: 0.283 AC: 1463 AN: 5178

South Asian (SAS) AF: 0.357 AC: 1723 AN: 4826

European-Finnish (FIN) AF: 0.226 AC: 2392 AN: 10598

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15909 AN: 67990

Other (OTH) AF: 0.195 AC: 412 AN: 2114

Alfa AF: 0.183 Hom.: 2113

Bravo AF: 0.179

Asia WGS AF: 0.257 AC: 894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.4
DANN	Benign	0.69
PhyloP100		0.0070
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: rs1568502; hg19: chr15-99487095;