rs166665

Variant names:

• chr7-23372179-A-C
• rs166665
• NM_006547.3:c.286-10438T>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.286-10438T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 151,594 control chromosomes in the GnomAD database, including 2,024 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 0.12 (2024 hom., cov: 31)
• Consequence: IGF2BP3 NM_006547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.605
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2BP3	NM_006547.3	c.286-10438T>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.286-10438T>G		intron_variant	Intron 3 of 14	1	NM_006547.3	ENSP00000258729.3

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17573 AN: 151476 Hom.: 2021 Cov.: 31

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.0743

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0306

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.0947

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

GnomAD4 genome AF: 0.116 AC: 17609 AN: 151594 Hom.: 2024 Cov.: 31 AF XY: 0.115 AC XY: 8548 AN XY: 74072

African (AFR) AF: 0.294 AC: 12131 AN: 41246

American (AMR) AF: 0.0744 AC: 1134 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 126 AN: 3468

East Asian (EAS) AF: 0.157 AC: 804 AN: 5122

South Asian (SAS) AF: 0.123 AC: 589 AN: 4806

European-Finnish (FIN) AF: 0.0306 AC: 321 AN: 10502

Middle Eastern (MID) AF: 0.0448 AC: 13 AN: 290

European-Non Finnish (NFE) AF: 0.0336 AC: 2283 AN: 67912

Other (OTH) AF: 0.0951 AC: 200 AN: 2102

Alfa AF: 0.0826 Hom.: 139

Bravo AF: 0.126

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.37
PhyloP100		-0.60
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: rs166665; hg19: chr7-23411798;