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
NM_001552.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.133
Publications
1 publications found
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]
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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 | c.357C>T | p.Asp119Asp | synonymous_variant | Exon 2 of 4 | ENST00000269593.5 | NP_001543.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0121 AC: 1847AN: 152108Hom.: 39 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1847
AN:
152108
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00309 AC: 663AN: 214232 AF XY: 0.00216 show subpopulations
GnomAD2 exomes
AF:
AC:
663
AN:
214232
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00118 AC: 1647AN: 1396298Hom.: 26 Cov.: 32 AF XY: 0.00103 AC XY: 713AN XY: 690596 show subpopulations
GnomAD4 exome
AF:
AC:
1647
AN:
1396298
Hom.:
Cov.:
32
AF XY:
AC XY:
713
AN XY:
690596
show subpopulations
African (AFR)
AF:
AC:
1359
AN:
30890
American (AMR)
AF:
AC:
88
AN:
37256
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24528
East Asian (EAS)
AF:
AC:
0
AN:
35138
South Asian (SAS)
AF:
AC:
7
AN:
78098
European-Finnish (FIN)
AF:
AC:
0
AN:
52350
Middle Eastern (MID)
AF:
AC:
4
AN:
5598
European-Non Finnish (NFE)
AF:
AC:
43
AN:
1074838
Other (OTH)
AF:
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: 1858AN: 152226Hom.: 39 Cov.: 32 AF XY: 0.0118 AC XY: 876AN XY: 74432 show subpopulations
GnomAD4 genome
AF:
AC:
1858
AN:
152226
Hom.:
Cov.:
32
AF XY:
AC XY:
876
AN XY:
74432
show subpopulations
African (AFR)
AF:
AC:
1773
AN:
41506
American (AMR)
AF:
AC:
63
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
1
AN:
5176
South Asian (SAS)
AF:
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
5
AN:
68014
Other (OTH)
AF:
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:
Hom.:
Bravo
AF:
Asia WGS
AF:
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:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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