rs2684773

chr15-98835915-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.641-55410T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,182 control chromosomes in the GnomAD database, including 4,252 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 (4252 hom., cov: 32)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368

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 = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1R	NM_000875.5	c.641-55410T>G		intron_variant		ENST00000650285.1
LOC124903561	XR_007064773.1	n.16246A>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1R	ENST00000650285.1	c.641-55410T>G		intron_variant			NM_000875.5	P4
	ENST00000689645.1	n.296+3876A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30552 AN: 152062 Hom.: 4214 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.201 AC: 30642 AN: 152182 Hom.: 4252 Cov.: 32 AF XY: 0.200 AC XY: 14909 AN XY: 74412

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.0965

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.209

Alfa AF: 0.156 Hom.: 758

Bravo AF: 0.211

Asia WGS AF: 0.184 AC: 641 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	1.1
Dann	Benign	0.73

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: rs2684773; hg19: chr15-99379144;