chr15-98948832-G-A

Position:

• chr15-98948832-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000875.5(IGF1R):​c.3722+124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,154,382 control chromosomes in the GnomAD database, including 30,273 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 0.18 (2820 hom., cov: 33)
  • Exomes 𝑓: 0.23 (27453 hom.)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.3722+124G>A		intron_variant		ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.3722+124G>A		intron_variant			NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000649865.1	c.3719+124G>A		intron_variant				ENSP00000496919.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27509 AN: 152122 Hom.: 2820 Cov.: 33

Gnomad AFR AF: 0.0767

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.188

GnomAD4 exome AF: 0.229 AC: 229520 AN: 1002142 Hom.: 27453 AF XY: 0.234 AC XY: 121213 AN XY: 517654

Gnomad4 AFR exome AF: 0.0746

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.249

Gnomad4 EAS exome AF: 0.308

Gnomad4 SAS exome AF: 0.326

Gnomad4 FIN exome AF: 0.206

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.181 AC: 27505 AN: 152240 Hom.: 2820 Cov.: 33 AF XY: 0.183 AC XY: 13621 AN XY: 74444

Gnomad4 AFR AF: 0.0766

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.185

Alfa AF: 0.0970 Hom.: 153

Bravo AF: 0.171

Asia WGS AF: 0.239 AC: 830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.56

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: rs17847195; hg19: chr15-99492061; COSMIC: COSV51309204; COSMIC: COSV51309204;