chr7-23396808-G-A

Position:

• chr7-23396808-G-A

Variant summary

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

The NM_006547.3(IGF2BP3):​c.285+21968C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,046 control chromosomes in the GnomAD database, including 4,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.25 (4905 hom., cov: 32)
• Consequence: IGF2BP3 NM_006547.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.726

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2BP3	NM_006547.3	c.285+21968C>T		intron_variant		ENST00000258729.8	NP_006538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2BP3	ENST00000258729.8	c.285+21968C>T		intron_variant		1	NM_006547.3	ENSP00000258729	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37702 AN: 151928 Hom.: 4896 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.248 AC: 37737 AN: 152046 Hom.: 4905 Cov.: 32 AF XY: 0.252 AC XY: 18734 AN XY: 74336

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.235

Alfa AF: 0.269 Hom.: 7314

Bravo AF: 0.235

Asia WGS AF: 0.247 AC: 859 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Vascular endothelial growth factor (VEGF) inhibitor response Other:1

association, no assertion criteria provided

case-control

Department of Ophthalmology, College of Medicine, Hanyang University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.59

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: rs12700428; hg19: chr7-23436427;