rs2684789

chr15-98948816-G-Achr15-98948816-G-Cchr15-98948816-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.3722+108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,302,414 control chromosomes in the GnomAD database, including 212,262 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 (23839 hom., cov: 32)
  • Exomes 𝑓: 0.57 (188423 hom.)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1R	NM_000875.5	c.3722+108G>A		intron_variant		ENST00000650285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1R	ENST00000650285.1	c.3722+108G>A		intron_variant			NM_000875.5	P4
IGF1R	ENST00000649865.1	c.3719+108G>A		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84795 AN: 151878 Hom.: 23822 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.555

GnomAD4 exome AF: 0.570 AC: 655891 AN: 1150418 Hom.: 188423 AF XY: 0.576 AC XY: 337862 AN XY: 586834

Gnomad4 AFR exome AF: 0.526

Gnomad4 AMR exome AF: 0.591

Gnomad4 ASJ exome AF: 0.608

Gnomad4 EAS exome AF: 0.703

Gnomad4 SAS exome AF: 0.702

Gnomad4 FIN exome AF: 0.532

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.574

GnomAD4 genome AF: 0.558 AC: 84843 AN: 151996 Hom.: 23839 Cov.: 32 AF XY: 0.562 AC XY: 41781 AN XY: 74302

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.548

Alfa AF: 0.556 Hom.: 34194

Bravo AF: 0.558

Asia WGS AF: 0.632 AC: 2199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.8
Dann	Benign	0.64

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: rs2684789; hg19: chr15-99492045;