7-23351827-A-G

Position:

• chr7-23351827-A-G

Variant summary

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

The ENST00000258729.8(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 ENST00000258729.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570

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=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2BP3	NM_006547.3	c.402-241T>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.402-241T>C		intron_variant		1	NM_006547.3	ENSP00000258729	P1

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

Gnomad4 AFR AF: 0.0758

Gnomad4 AMR AF: 0.0455

Gnomad4 ASJ AF: 0.0432

Gnomad4 EAS AF: 0.00831

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0258

Gnomad4 NFE AF: 0.0198

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0364 Hom.: 21

Bravo AF: 0.0422

Asia WGS AF: 0.0650 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.3
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs274057; hg19: chr7-23391446;