rs2684774

chr15-98836794-T-G

Variant summary

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

The NM_000875.5(IGF1R):c.641-54531T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,160 control chromosomes in the GnomAD database, including 4,361 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 0.20 (4361 hom., cov: 32)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.643

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]

LOC124903561 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1R	NM_000875.5	c.641-54531T>G		intron_variant		ENST00000650285.1
LOC124903561	XR_007064773.1	n.15367A>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1R	ENST00000650285.1	c.641-54531T>G		intron_variant			NM_000875.5	P4
	ENST00000689645.1	n.296+2997A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30992 AN: 152040 Hom.: 4322 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.204 AC: 31084 AN: 152160 Hom.: 4361 Cov.: 32 AF XY: 0.203 AC XY: 15120 AN XY: 74402

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.0993

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.210

Alfa AF: 0.174 Hom.: 391

Bravo AF: 0.214

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	4.3
Dann	Benign	0.81

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: rs2684774; hg19: chr15-99380023;