rs6777038

Positions:

• chr3-185723172-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006548.6(IGF2BP2):​c.240-24825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,188 control chromosomes in the GnomAD database, including 1,115 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 0.11 (1115 hom., cov: 32)
• Consequence: IGF2BP2 NM_006548.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.57

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]

IGF2BP2-AS1 (HGNC:32674): (IGF2BP2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2BP2	NM_006548.6	c.240-24825G>A		intron_variant		ENST00000382199.7	NP_006539.3
IGF2BP2-AS1	NR_126326.1	n.796+639C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2BP2	ENST00000382199.7	c.240-24825G>A		intron_variant		1	NM_006548.6	ENSP00000371634	P1
IGF2BP2-AS1	ENST00000456447.5	n.796+639C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16668 AN: 152070 Hom.: 1123 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0872

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.0499

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.110 AC: 16666 AN: 152188 Hom.: 1115 Cov.: 32 AF XY: 0.111 AC XY: 8277 AN XY: 74410

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0870

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.0499

Gnomad4 NFE AF: 0.0922

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0967 Hom.: 287

Bravo AF: 0.106

Asia WGS AF: 0.254 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.83

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: rs6777038; hg19: chr3-185440960;