chr15-98769512-A-G

Variant names:

• chr15-98769512-A-G
• rs2137680
• NM_000875.5:c.640+61405A>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.640+61405A>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 152,032 control chromosomes in the GnomAD database, including 29,265 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 (29265 hom., cov: 32)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.640+61405A>G		intron_variant	Intron 2 of 20	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.640+61405A>G		intron_variant	Intron 2 of 20		NM_000875.5	ENSP00000497069.1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91478 AN: 151914 Hom.: 29263 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.602 AC: 91480 AN: 152032 Hom.: 29265 Cov.: 32 AF XY: 0.602 AC XY: 44724 AN XY: 74302

African (AFR) AF: 0.363 AC: 15046 AN: 41466

American (AMR) AF: 0.679 AC: 10375 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2583 AN: 3470

East Asian (EAS) AF: 0.558 AC: 2884 AN: 5166

South Asian (SAS) AF: 0.570 AC: 2744 AN: 4818

European-Finnish (FIN) AF: 0.729 AC: 7680 AN: 10538

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.708 AC: 48124 AN: 67980

Other (OTH) AF: 0.593 AC: 1255 AN: 2116

Alfa AF: 0.633 Hom.: 3927

Bravo AF: 0.591

Asia WGS AF: 0.508 AC: 1767 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	0.89
DANN	Benign	0.54
PhyloP100		-0.52
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: rs2137680; hg19: chr15-99312741;