chr7-23440848-C-T

Variant names:

• chr7-23440848-C-T
• rs11763760
• NM_006547.3:c.237-22024G>A

Variant summary

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

The NM_006547.3(IGF2BP3):​c.237-22024G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,188 control chromosomes in the GnomAD database, including 2,455 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 0.17 (2455 hom., cov: 32)
• Consequence: IGF2BP3 NM_006547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.22
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2BP3	NM_006547.3	c.237-22024G>A		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.237-22024G>A		intron_variant	Intron 2 of 14	1	NM_006547.3	ENSP00000258729.3

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25636 AN: 152070 Hom.: 2455 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.168 AC: 25639 AN: 152188 Hom.: 2455 Cov.: 32 AF XY: 0.167 AC XY: 12398 AN XY: 74410

African (AFR) AF: 0.107 AC: 4445 AN: 41524

American (AMR) AF: 0.153 AC: 2340 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3470

East Asian (EAS) AF: 0.0104 AC: 54 AN: 5182

South Asian (SAS) AF: 0.271 AC: 1309 AN: 4828

European-Finnish (FIN) AF: 0.158 AC: 1670 AN: 10592

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14318 AN: 67998

Other (OTH) AF: 0.191 AC: 404 AN: 2110

Alfa AF: 0.188 Hom.: 4302

Bravo AF: 0.163

Asia WGS AF: 0.133 AC: 469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.78
PhyloP100		-3.2
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: rs11763760; hg19: chr7-23480467; COSMIC: COSV51694560;