NM_006547.3:c.286-19407T>G

Variant names:

• chr7-23381148-A-C
• rs375092
• NM_006547.3:c.286-19407T>G

Variant summary

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

The NM_006547.3(IGF2BP3):​c.286-19407T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,128 control chromosomes in the GnomAD database, including 13,463 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 0.33 (13463 hom., cov: 32)
• Consequence: IGF2BP3 NM_006547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2BP3	NM_006547.3	c.286-19407T>G		intron_variant	Intron 3 of 14	ENST00000258729.8	NP_006538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2BP3	ENST00000258729.8	c.286-19407T>G		intron_variant	Intron 3 of 14	1	NM_006547.3	ENSP00000258729.3

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50126 AN: 152010 Hom.: 13417 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.330 AC: 50235 AN: 152128 Hom.: 13463 Cov.: 32 AF XY: 0.325 AC XY: 24172 AN XY: 74378

African (AFR) AF: 0.743 AC: 30826 AN: 41486

American (AMR) AF: 0.222 AC: 3387 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 950 AN: 3472

East Asian (EAS) AF: 0.191 AC: 990 AN: 5172

South Asian (SAS) AF: 0.308 AC: 1481 AN: 4812

European-Finnish (FIN) AF: 0.121 AC: 1288 AN: 10602

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10459 AN: 67986

Other (OTH) AF: 0.316 AC: 668 AN: 2114

Alfa AF: 0.219 Hom.: 17798

Bravo AF: 0.355

Asia WGS AF: 0.309 AC: 1077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.40
PhyloP100		-0.37
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)		0.0		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: rs375092; hg19: chr7-23420767;