rs4686692

Positions:

• chr3-185763280-C-T

Variant summary

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

The NM_006548.6(IGF2BP2):​c.239+59873G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,194 control chromosomes in the GnomAD database, including 57,429 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 0.87 (57429 hom., cov: 31)
• Consequence: IGF2BP2 NM_006548.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303

Genes affected

IGF2BP2 (HGNC:28867): (insulin like growth factor 2 mRNA binding protein 2) This gene encodes a protein that binds the 5' UTR of insulin-like growth factor 2 (IGF2) mRNA and regulates its translation. It plays an important role in metabolism and variation in this gene is associated with susceptibility to diabetes. Alternative splicing and promoter usage results in multiple transcript variants. Related pseudogenes are found on several chromosomes. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2BP2	NM_006548.6	c.239+59873G>A		intron_variant		ENST00000382199.7	NP_006539.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2BP2	ENST00000382199.7	c.239+59873G>A		intron_variant		1	NM_006548.6	ENSP00000371634	P1

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131536 AN: 152076 Hom.: 57368 Cov.: 31

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.865 AC: 131657 AN: 152194 Hom.: 57429 Cov.: 31 AF XY: 0.869 AC XY: 64661 AN XY: 74408

Gnomad4 AFR AF: 0.964

Gnomad4 AMR AF: 0.888

Gnomad4 ASJ AF: 0.873

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.928

Gnomad4 FIN AF: 0.830

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.852

Alfa AF: 0.819 Hom.: 26003

Bravo AF: 0.872

Asia WGS AF: 0.969 AC: 3366 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.27

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: rs4686692; hg19: chr3-185481068;