Genetic Variant NM_001552.3:c.23C>T (chr17-40443758-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001552.3(IGFBP4):c.23C>T(p.Ala8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,497,934 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

IGFBP4
NM_001552.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.991

Publications

0 publications found

Variant links:

Genes affected

IGFBP4 (HGNC:5473): (insulin like growth factor binding protein 4) 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 binds both insulin-like growth factors (IGFs) I and II and circulates in the plasma in both glycosylated and non-glycosylated forms. Binding of this protein prolongs the half-life of the IGFs and alters their interaction with cell surface receptors. [provided by RefSeq, Jul 2008]

IGFBP4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14067426).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001552.3. 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
	IGFBP4	NM_001552.3	MANE Select	c.23C>T	p.Ala8Val	missense	Exon 1 of 4	NP_001543.2	P22692-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGFBP4	ENST00000269593.5	TSL:1 MANE Select	c.23C>T	p.Ala8Val	missense	Exon 1 of 4	ENSP00000269593.4	P22692-1
IGFBP4	ENST00000941634.1		c.23C>T	p.Ala8Val	missense	Exon 1 of 4	ENSP00000611693.1
IGFBP4	ENST00000906679.1		c.23C>T	p.Ala8Val	missense	Exon 1 of 4	ENSP00000576738.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151612

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000163

AC:

AN:

1346322

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

664278

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26950

American (AMR)

AF:

0.00

AC:

AN:

31324

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23536

East Asian (EAS)

AF:

0.00

AC:

AN:

31300

South Asian (SAS)

AF:

0.00

AC:

AN:

75544

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3940

European-Non Finnish (NFE)

AF:

0.0000197

AC:

AN:

1064494

Other (OTH)

AF:

0.0000179

AC:

AN:

55998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151612

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74054

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41334

American (AMR)

AF:

0.00

AC:

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10424

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67868

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

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

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.51

M_CAP

Benign

0.077

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

PhyloP100

0.99

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.58

REVEL

Benign

0.030

Sift

Uncertain

0.010

Sift4G

Benign

0.18

Polyphen

0.0

Vest4

0.12

MutPred

0.39

Loss of helix (P = 0.028)

MVP

0.42

MPC

0.67

ClinPred

0.30

GERP RS

1.4

PromoterAI

-0.058

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.41

Mutation Taster

=86/14

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over