rs12540730

Positions:

• chr7-23444196-A-G

Variant summary

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

The NM_006547.3(IGF2BP3):​c.236+24286T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,034 control chromosomes in the GnomAD database, including 2,892 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 (2892 hom., cov: 31)
• Consequence: IGF2BP3 NM_006547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2BP3	NM_006547.3	c.236+24286T>C		intron_variant		ENST00000258729.8	NP_006538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2BP3	ENST00000258729.8	c.236+24286T>C		intron_variant		1	NM_006547.3	ENSP00000258729	P1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27769 AN: 151916 Hom.: 2892 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.183 AC: 27770 AN: 152034 Hom.: 2892 Cov.: 31 AF XY: 0.182 AC XY: 13491 AN XY: 74322

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.202

Alfa AF: 0.222 Hom.: 7959

Bravo AF: 0.174

Asia WGS AF: 0.135 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs12540730; hg19: chr7-23483815;