ENST00000448817.1:c.-376A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000448817.1(IGFBP3):​c.-376A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,252 control chromosomes in the GnomAD database, including 38,919 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.71 ( 38919 hom., cov: 35)

Consequence

IGFBP3
ENST00000448817.1 upstream_gene

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

16 publications found
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]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IGFBP3ENST00000448817.1 linkc.-376A>G upstream_gene_variant 4 ENSP00000389668.1 C9JMX4

Frequencies

GnomAD3 genomes
AF:
0.712
AC:
108360
AN:
152134
Hom.:
38905
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.722
Gnomad AMI
AF:
0.774
Gnomad AMR
AF:
0.759
Gnomad ASJ
AF:
0.649
Gnomad EAS
AF:
0.966
Gnomad SAS
AF:
0.669
Gnomad FIN
AF:
0.745
Gnomad MID
AF:
0.658
Gnomad NFE
AF:
0.677
Gnomad OTH
AF:
0.698
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.712
AC:
108423
AN:
152252
Hom.:
38919
Cov.:
35
AF XY:
0.716
AC XY:
53314
AN XY:
74436
show subpopulations
African (AFR)
AF:
0.722
AC:
29997
AN:
41536
American (AMR)
AF:
0.760
AC:
11627
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
0.649
AC:
2255
AN:
3472
East Asian (EAS)
AF:
0.966
AC:
5010
AN:
5186
South Asian (SAS)
AF:
0.668
AC:
3219
AN:
4820
European-Finnish (FIN)
AF:
0.745
AC:
7900
AN:
10606
Middle Eastern (MID)
AF:
0.663
AC:
195
AN:
294
European-Non Finnish (NFE)
AF:
0.677
AC:
46054
AN:
68012
Other (OTH)
AF:
0.692
AC:
1462
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1679
3359
5038
6718
8397
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
832
1664
2496
3328
4160
<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:
0.688
Hom.:
6572
Bravo
AF:
0.718
Asia WGS
AF:
0.779
AC:
2707
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
2.8
DANN
Benign
0.46
PhyloP100
-1.2
PromoterAI
0.069
Neutral

Splicing

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

Publications

Other links and lift over

dbSNP: rs2132571; hg19: chr7-45961674; API