Variant 17-48999124-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006546.4(IGF2BP1):c.191A>G(p.Gln64Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000394 in 1,394,658 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000039 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IGF2BP1
NM_006546.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.10

Variant links:

Genes affected

IGF2BP1 (HGNC:28866): (insulin like growth factor 2 mRNA binding protein 1) This gene encodes a member of the insulin-like growth factor 2 mRNA-binding protein family. The protein encoded by this gene contains four K homology domains and two RNA recognition motifs. It functions by binding to the mRNAs of certain genes, including insulin-like growth factor 2, beta-actin and beta-transducin repeat-containing protein, and regulating their translation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

IGF2BP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22616062).

BS2

High AC in GnomAdExome4 at 55 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2BP1	NM_006546.4 linkuse as main transcript	c.191A>G	p.Gln64Arg	missense_variant	2/15	ENST00000290341.8	NP_006537.3	Q9NZI8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IGF2BP1	ENST00000290341.8 linkuse as main transcript	c.191A>G	p.Gln64Arg	missense_variant	2/15	1	NM_006546.4	ENSP00000290341.3	Q9NZI8-1
IGF2BP1	ENST00000431824.2 linkuse as main transcript	c.191A>G	p.Gln64Arg	missense_variant	2/13	1		ENSP00000389135.2	Q9NZI8-2
IGF2BP1	ENST00000510023.5 linkuse as main transcript	n.451A>G		non_coding_transcript_exon_variant	2/3	3
IGF2BP1	ENST00000515586.5 linkuse as main transcript	n.174A>G		non_coding_transcript_exon_variant	2/6	3

Frequencies

GnomAD3 genomes

AF:

0.0000204

AC:

AN:

147170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000299

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000442

AC:

AN:

248866

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000621

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000394

AC:

AN:

1394658

Hom.:

Cov.:

AF XY:

0.0000504

AC XY:

AN XY:

694556

show subpopulations

Gnomad4 AFR exome

AF:

0.0000951

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000609

Gnomad4 SAS exome

AF:

0.0000820

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000197

Gnomad4 OTH exome

AF:

0.000124

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000204

AC:

AN:

147170

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71570

show subpopulations

Gnomad4 AFR

AF:

0.0000252

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000299

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000238

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2024

The c.191A>G (p.Q64R) alteration is located in exon 2 (coding exon 2) of the IGF2BP1 gene. This alteration results from a A to G substitution at nucleotide position 191, causing the glutamine (Q) at amino acid position 64 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.096

T;.

Eigen

Benign

0.028

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0066

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.48

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.025

D;D

Sift4G

Benign

0.063

T;D

Polyphen

0.0030

B;.

Vest4

0.25

MutPred

0.44

Gain of MoRF binding (P = 0.0224);Gain of MoRF binding (P = 0.0224);

MVP

0.46

MPC

0.97

ClinPred

0.18

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over