Variant rs2854746 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000598.5(IGFBP3):c.95C>T(p.Ala32Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000486 in 1,441,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A32G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

IGFBP3
NM_000598.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.359

Variant links:

Genes affected

IGFBP3 (HGNC:5472): (insulin like growth factor binding protein 3) This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

IGFBP3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059669197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IGFBP3	NM_000598.5 linkuse as main transcript	c.95C>T	p.Ala32Val	missense_variant	1/5	ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2 linkuse as main transcript	c.95C>T	p.Ala32Val	missense_variant	1/5		NP_001013416.1
IGFBP3	XM_047420325.1 linkuse as main transcript	c.95C>T	p.Ala32Val	missense_variant	1/4		XP_047276281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000613132.5 linkuse as main transcript	c.95C>T	p.Ala32Val	missense_variant	1/5	5	NM_000598.5	ENSP00000477772	P4	P17936-1
IGFBP3	ENST00000381083.9 linkuse as main transcript	c.95C>T	p.Ala32Val	missense_variant	1/5	5		ENSP00000370473	A1	P17936-2
IGFBP3	ENST00000381086.9 linkuse as main transcript	c.9+86C>T		intron_variant		2		ENSP00000370476
IGFBP3	ENST00000448817.1 linkuse as main transcript	c.73+581C>T		intron_variant		4		ENSP00000389668

Frequencies

GnomAD3 genomes

AF:

0.0000661

AC:

AN:

151250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.000133

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1289990

Hom.:

Cov.:

AF XY:

0.0000457

AC XY:

AN XY:

635014

show subpopulations

Gnomad4 AFR exome

AF:

0.0000786

Gnomad4 AMR exome

AF:

0.0000930

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000482

Gnomad4 OTH exome

AF:

0.0000939

GnomAD4 genome

AF:

0.0000661

AC:

AN:

151250

Hom.:

Cov.:

AF XY:

0.0000812

AC XY:

AN XY:

73878

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.000133

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.27

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.26

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.022

Sift

Benign

0.54

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.071

B;.

Vest4

0.077

MutPred

0.22

Loss of relative solvent accessibility (P = 0.0981);Loss of relative solvent accessibility (P = 0.0981);

MVP

0.32

MPC

0.34

ClinPred

0.027

GERP RS

0.63

Varity_R

0.032

gMVP

0.42

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over