15-98769625-A-G

Variant names:

• chr15-98769625-A-G
• rs2175795
• NM_000875.5:c.640+61518A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000875.5(IGF1R):​c.640+61518A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 152,078 control chromosomes in the GnomAD database, including 29,278 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 0.60 (29278 hom., cov: 33)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 2 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

LOC124903560 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000875.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	NM_000875.5	MANE Select	c.640+61518A>G		intron	N/A	NP_000866.1
	IGF1R	NM_001291858.2		c.640+61518A>G		intron	N/A	NP_001278787.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	ENST00000650285.1	MANE Select	c.640+61518A>G		intron	N/A	ENSP00000497069.1
	IGF1R	ENST00000559925.5	TSL:1	n.640+61518A>G		intron	N/A
	IGF1R	ENST00000649865.1		c.640+61518A>G		intron	N/A	ENSP00000496919.1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91513 AN: 151962 Hom.: 29276 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.602 AC: 91514 AN: 152078 Hom.: 29278 Cov.: 33 AF XY: 0.602 AC XY: 44740 AN XY: 74330

African (AFR) AF: 0.363 AC: 15054 AN: 41474

American (AMR) AF: 0.679 AC: 10383 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2576 AN: 3464

East Asian (EAS) AF: 0.557 AC: 2875 AN: 5166

South Asian (SAS) AF: 0.570 AC: 2749 AN: 4822

European-Finnish (FIN) AF: 0.729 AC: 7710 AN: 10574

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48123 AN: 67976

Other (OTH) AF: 0.594 AC: 1253 AN: 2110

Alfa AF: 0.560 Hom.: 2153

Bravo AF: 0.591

Asia WGS AF: 0.508 AC: 1767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	9.4
DANN	Benign	0.85
PhyloP100		1.1
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: rs2175795; hg19: chr15-99312854;