dbSNP rs145056288: IGF2BP3:p.Val522Ile (chr7-23312812-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006547.3(IGF2BP3):c.1564G>A(p.Val522Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000768 in 1,612,368 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 2 hom. )

Consequence

IGF2BP3
NM_006547.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.12

Publications

2 publications found

Variant links:

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]

IGF2BP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022533685).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006547.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2BP3	NM_006547.3	MANE Select	c.1564G>A	p.Val522Ile	missense	Exon 14 of 15	NP_006538.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGF2BP3	ENST00000258729.8	TSL:1 MANE Select	c.1564G>A	p.Val522Ile	missense	Exon 14 of 15	ENSP00000258729.3	O00425-1
IGF2BP3	ENST00000619562.4	TSL:1	c.421G>A	p.Val141Ile	missense	Exon 7 of 8	ENSP00000480267.1	O00425-2
IGF2BP3	ENST00000922496.1		c.646G>A	p.Val216Ile	missense	Exon 7 of 8	ENSP00000592555.1

Frequencies

GnomAD3 genomes

AF:

0.000572

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000693

AC:

173

AN:

249542

AF XY:

0.000623

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000559

Gnomad ASJ exome

AF:

0.00359

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000936

Gnomad OTH exome

AF:

0.000819

GnomAD4 exome

AF:

0.000789

AC:

1152

AN:

1460030

Hom.:

Cov.:

AF XY:

0.000723

AC XY:

525

AN XY:

726300

show subpopulations

African (AFR)

AF:

0.000210

AC:

AN:

33394

American (AMR)

AF:

0.000543

AC:

AN:

44202

Ashkenazi Jewish (ASJ)

AF:

0.00322

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

85744

European-Finnish (FIN)

AF:

0.000169

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.000701

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.000848

AC:

943

AN:

1111470

Other (OTH)

AF:

0.00134

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

112

168

224

280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000571

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41586

American (AMR)

AF:

0.000196

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000897

AC:

AN:

68030

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000261

Hom.:

Bravo

AF:

0.000684

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000642

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.000949

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.031

Eigen

Benign

0.029

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0051

MetaRNN

Benign

0.023

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.22

PhyloP100

6.1

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.35

REVEL

Benign

0.12

Sift

Benign

0.57

Sift4G

Benign

0.23

Polyphen

0.025

Vest4

0.56

MVP

0.33

MPC

0.67

ClinPred

0.017

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.086

gMVP

0.28

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over