rs12534093

Variant names:

• chr7-23463355-T-A
• rs12534093
• NM_006547.3:c.236+5127A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006547.3(IGF2BP3):​c.236+5127A>T variant causes a intron change. The variant allele was found at a frequency of 0.182 in 152,190 control chromosomes in the GnomAD database, including 2,890 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 0.18 (2890 hom., cov: 33)
• Consequence: IGF2BP3 NM_006547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.65
• Publications: 44 publications found

Genes affected

IGF2BP3 (HGNC:28868): (insulin like growth factor 2 mRNA binding protein 3) The protein encoded by this gene is primarily found in the nucleolus, where it can bind to the 5' UTR of the insulin-like growth factor II leader 3 mRNA and may repress translation of insulin-like growth factor II during late development. The encoded protein contains several KH domains, which are important in RNA binding and are known to be involved in RNA synthesis and metabolism. A pseudogene exists on chromosome 7, and there are putative pseudogenes on other chromosomes. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2BP3	NM_006547.3	c.236+5127A>T		intron_variant	Intron 2 of 14	ENST00000258729.8	NP_006538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2BP3	ENST00000258729.8	c.236+5127A>T		intron_variant	Intron 2 of 14	1	NM_006547.3	ENSP00000258729.3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27736 AN: 152072 Hom.: 2891 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.182 AC: 27738 AN: 152190 Hom.: 2890 Cov.: 33 AF XY: 0.181 AC XY: 13435 AN XY: 74394

African (AFR) AF: 0.115 AC: 4757 AN: 41530

American (AMR) AF: 0.166 AC: 2544 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 963 AN: 3472

East Asian (EAS) AF: 0.0119 AC: 62 AN: 5192

South Asian (SAS) AF: 0.302 AC: 1455 AN: 4820

European-Finnish (FIN) AF: 0.170 AC: 1799 AN: 10574

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15529 AN: 68004

Other (OTH) AF: 0.211 AC: 445 AN: 2108

Alfa AF: 0.217 Hom.: 2101

Bravo AF: 0.176

Asia WGS AF: 0.143 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		3.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12534093; hg19: chr7-23502974;