15-98660267-C-T

Position:

• chr15-98660267-C-T

Variant summary

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

The NM_000875.5(IGF1R):​c.94+10592C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,114 control chromosomes in the GnomAD database, including 8,110 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 0.30 (8108 hom., cov: 33)
  • Exomes 𝑓: 0.21 (2 hom.)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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]

ENSG00000278022 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.94+10592C>T		intron_variant		ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.94+10592C>T		intron_variant			NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000559925.5	n.94+10592C>T		intron_variant		1
IGF1R	ENST00000649865.1	c.94+10592C>T		intron_variant				ENSP00000496919.1
ENSG00000278022	ENST00000618697.1	n.58C>T		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45505 AN: 151946 Hom.: 8101 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.212 AC: 11 AN: 52 Hom.: 2 Cov.: 0 AF XY: 0.214 AC XY: 6 AN XY: 28

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.299 AC: 45515 AN: 152062 Hom.: 8108 Cov.: 33 AF XY: 0.304 AC XY: 22625 AN XY: 74308

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.292

Alfa AF: 0.362 Hom.: 20948

Bravo AF: 0.278

Asia WGS AF: 0.349 AC: 1215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.8
DANN	Benign	0.85

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: rs4966009; hg19: chr15-99203496;