NM_006547.3:c.286-595C>A

Variant names:

• chr7-23362336-G-T
• rs433395
• NM_006547.3:c.286-595C>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.286-595C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 152,070 control chromosomes in the GnomAD database, including 24,369 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 0.53 (24369 hom., cov: 32)
• Consequence: IGF2BP3 NM_006547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.68
• Publications: 19 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2BP3	NM_006547.3	c.286-595C>A		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.286-595C>A		intron_variant	Intron 3 of 14	1	NM_006547.3	ENSP00000258729.3

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80015 AN: 151952 Hom.: 24306 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.527 AC: 80137 AN: 152070 Hom.: 24369 Cov.: 32 AF XY: 0.522 AC XY: 38827 AN XY: 74320

African (AFR) AF: 0.850 AC: 35297 AN: 41512

American (AMR) AF: 0.411 AC: 6278 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1638 AN: 3468

East Asian (EAS) AF: 0.228 AC: 1175 AN: 5160

South Asian (SAS) AF: 0.383 AC: 1844 AN: 4816

European-Finnish (FIN) AF: 0.403 AC: 4259 AN: 10556

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28135 AN: 67970

Other (OTH) AF: 0.511 AC: 1079 AN: 2112

Alfa AF: 0.449 Hom.: 52250

Bravo AF: 0.537

Asia WGS AF: 0.402 AC: 1399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.069
DANN	Benign	0.53
PhyloP100		-4.7
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: rs433395; hg19: chr7-23401955;