17-40452992-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001552.3(IGFBP4):c.357C>T(p.Asp119Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 1,548,524 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 39 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 26 hom. )

Consequence

IGFBP4
NM_001552.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.133

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 17-40452992-C-T is Benign according to our data. Variant chr17-40452992-C-T is described in CliVar as Benign. Clinvar id is 710464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-40452992-C-T is described in CliVar as Benign. Clinvar id is 710464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-40452992-C-T is described in CliVar as Benign. Clinvar id is 710464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-40452992-C-T is described in CliVar as Benign. Clinvar id is 710464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-40452992-C-T is described in CliVar as Benign. Clinvar id is 710464.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-40452992-C-T is described in CliVar as Benign. Clinvar id is 710464.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.133 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0122 (1858/152226) while in subpopulation AFR AF = 0.0427 (1773/41506). AF 95% confidence interval is 0.0411. There are 39 homozygotes in GnomAd4. There are 876 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP4	NM_001552.3 link	c.357C>T	p.Asp119Asp	synonymous_variant	Exon 2 of 4	ENST00000269593.5	NP_001543.2	P22692-1A0A024R1U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP4	ENST00000269593.5 link	c.357C>T	p.Asp119Asp	synonymous_variant	Exon 2 of 4	1	NM_001552.3	ENSP00000269593.4		P22692-1

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

1847

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0426

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.00309

AC:

663

AN:

214232

AF XY:

0.00216

show subpopulations

Gnomad AFR exome

AF:

0.0423

Gnomad AMR exome

AF:

0.00251

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000724

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000299

Gnomad OTH exome

AF:

0.000804

GnomAD4 exome

AF:

0.00118

AC:

1647

AN:

1396298

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

713

AN XY:

690596

show subpopulations

African (AFR)

AF:

0.0440

AC:

1359

AN:

30890

American (AMR)

AF:

0.00236

AC:

AN:

37256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24528

East Asian (EAS)

AF:

0.00

AC:

AN:

35138

South Asian (SAS)

AF:

0.0000896

AC:

AN:

78098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52350

Middle Eastern (MID)

AF:

0.000715

AC:

AN:

5598

European-Non Finnish (NFE)

AF:

0.0000400

AC:

AN:

1074838

Other (OTH)

AF:

0.00253

AC:

146

AN:

57602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

146

218

291

364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.0122

AC:

1858

AN:

152226

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

876

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0427

AC:

1773

AN:

41506

American (AMR)

AF:

0.00412

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68014

Other (OTH)

AF:

0.00758

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

172

259

345

431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00537

Hom.:

Bravo

AF:

0.0139

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

7.0

(source)

DANN

Benign

0.66

PhyloP100

0.13

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over