rs12540724
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_000598.5(IGFBP3):c.404-264T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 152,310 control chromosomes in the GnomAD database, including 60 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 0.023 ( 60 hom., cov: 32)
Consequence
IGFBP3
NM_000598.5 intron
NM_000598.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.708
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 made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0233 (3550/152310) while in subpopulation NFE AF= 0.0355 (2414/68024). AF 95% confidence interval is 0.0343. There are 60 homozygotes in gnomad4. There are 1739 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 60 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGFBP3 | NM_000598.5 | c.404-264T>C | intron_variant | ENST00000613132.5 | |||
IGFBP3 | NM_001013398.2 | c.422-264T>C | intron_variant | ||||
IGFBP3 | XM_047420325.1 | c.404-264T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGFBP3 | ENST00000613132.5 | c.404-264T>C | intron_variant | 5 | NM_000598.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0233 AC: 3549AN: 152192Hom.: 60 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.0233 AC: 3550AN: 152310Hom.: 60 Cov.: 32 AF XY: 0.0233 AC XY: 1739AN XY: 74478
GnomAD4 genome
?
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3550
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74478
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3478
ClinVar
Not reported inComputational scores
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Name
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at