17-40452992-C-T

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

2

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]

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
IGFBP4NM_001552.3 linkc.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
IGFBP4ENST00000269593.5 linkc.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.:
39
Cov.:
32
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.:
26
Cov.:
32
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:
88
AN:
37256
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24528
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35138
South Asian (SAS)
AF:
0.0000896
AC:
7
AN:
78098
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52350
Middle Eastern (MID)
AF:
0.000715
AC:
4
AN:
5598
European-Non Finnish (NFE)
AF:
0.0000400
AC:
43
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
0
73
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
0
46
92
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.:
39
Cov.:
32
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:
63
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5176
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000735
AC:
5
AN:
68014
Other (OTH)
AF:
0.00758
AC:
16
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.496
Heterozygous variant carriers
0
86
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
0
20
40
60
80
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.:
9
Bravo
AF:
0.0139
Asia WGS
AF:
0.00606
AC:
21
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
DANN
Benign
0.66
PhyloP100
0.13
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs79982277; hg19: chr17-38609244; API