7-23351827-A-G

Variant names:

• chr7-23351827-A-G
• rs274057
• NM_006547.3:c.402-241T>C

Variant summary

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

The NM_006547.3(IGF2BP3):​c.402-241T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0411 in 152,244 control chromosomes in the GnomAD database, including 211 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 0.041 (211 hom., cov: 31)
• Consequence: IGF2BP3 NM_006547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570
• Publications: 5 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=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0978 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006547.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2BP3	NM_006547.3	MANE Select	c.402-241T>C		intron	N/A	NP_006538.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2BP3	ENST00000258729.8	TSL:1 MANE Select	c.402-241T>C		intron	N/A	ENSP00000258729.3
	IGF2BP3	ENST00000421467.6	TSL:5	n.*55-241T>C		intron	N/A	ENSP00000395936.1
	IGF2BP3	ENST00000465058.5	TSL:4	n.392-241T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0411 AC: 6248 AN: 152126 Hom.: 212 Cov.: 31

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0452

Gnomad ASJ AF: 0.0432

Gnomad EAS AF: 0.00848

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0364

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

GnomAD4 genome AF: 0.0411 AC: 6259 AN: 152244 Hom.: 211 Cov.: 31 AF XY: 0.0431 AC XY: 3207 AN XY: 74444

African (AFR) AF: 0.0758 AC: 3149 AN: 41526

American (AMR) AF: 0.0455 AC: 696 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0432 AC: 150 AN: 3472

East Asian (EAS) AF: 0.00831 AC: 43 AN: 5174

South Asian (SAS) AF: 0.105 AC: 508 AN: 4822

European-Finnish (FIN) AF: 0.0258 AC: 274 AN: 10612

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0198 AC: 1348 AN: 68018

Other (OTH) AF: 0.0360 AC: 76 AN: 2112

Alfa AF: 0.0380 Hom.: 25

Bravo AF: 0.0422

Asia WGS AF: 0.0650 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.3
DANN	Benign	0.58
PhyloP100		0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs274057; hg19: chr7-23391446;