rs12438493

chr15-98933816-G-Achr15-98933816-G-Cchr15-98933816-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.2957-1008G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,444 control chromosomes in the GnomAD database, including 15,847 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 0.46 (15847 hom., cov: 31)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1R	NM_000875.5	c.2957-1008G>A		intron_variant		ENST00000650285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1R	ENST00000650285.1	c.2957-1008G>A		intron_variant			NM_000875.5	P4
IGF1R	ENST00000560972.1	n.260-1500G>A		intron_variant, non_coding_transcript_variant		1
IGF1R	ENST00000649865.1	c.2954-1008G>A		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 68999 AN: 151326 Hom.: 15838 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.456 AC: 69049 AN: 151444 Hom.: 15847 Cov.: 31 AF XY: 0.451 AC XY: 33380 AN XY: 73994

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.422

Alfa AF: 0.353 Hom.: 1171

Bravo AF: 0.460

Asia WGS AF: 0.340 AC: 1181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.23
Dann	Benign	0.72

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: rs12438493; hg19: chr15-99477045;