rs8034284

Positions:

• chr15-98953019-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.3723-4042C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,038 control chromosomes in the GnomAD database, including 21,671 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 0.53 (21668 hom., cov: 32)
  • Exomes 𝑓: 0.55 (3 hom.)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.3723-4042C>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.3723-4042C>T		intron_variant			NM_000875.5	ENSP00000497069	P4
IGF1R	ENST00000649865.1	c.3720-4042C>T		intron_variant				ENSP00000496919	A1
IGF1R	ENST00000558751.1	n.225C>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80050 AN: 151898 Hom.: 21642 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.488

GnomAD4 exome AF: 0.545 AC: 12 AN: 22 Hom.: 3 Cov.: 0 AF XY: 0.429 AC XY: 6 AN XY: 14

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.527 AC: 80125 AN: 152016 Hom.: 21668 Cov.: 32 AF XY: 0.524 AC XY: 38913 AN XY: 74308

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.484

Alfa AF: 0.487 Hom.: 9380

Bravo AF: 0.544

Asia WGS AF: 0.494 AC: 1722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.41

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: rs8034284; hg19: chr15-99496248;