10-93593832-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 4P and 9B. PM1PM2BP4_StrongBP6BS1
The NM_006744.4(RBP4):c.559G>A(p.Val187Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,611,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006744.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBP4 | NM_006744.4 | c.559G>A | p.Val187Ile | missense_variant | 5/6 | ENST00000371464.8 | |
RBP4 | NM_001323517.1 | c.559G>A | p.Val187Ile | missense_variant | 5/6 | ||
RBP4 | NM_001323518.2 | c.553G>A | p.Val185Ile | missense_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBP4 | ENST00000371464.8 | c.559G>A | p.Val187Ile | missense_variant | 5/6 | 1 | NM_006744.4 | P1 | |
RBP4 | ENST00000371467.5 | c.559G>A | p.Val187Ile | missense_variant | 5/6 | 5 | P1 | ||
RBP4 | ENST00000371469.2 | c.553G>A | p.Val185Ile | missense_variant | 5/6 | 5 | |||
FFAR4 | ENST00000604414.1 | c.697-10242C>T | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000104 AC: 26AN: 250672Hom.: 0 AF XY: 0.0000738 AC XY: 10AN XY: 135546
GnomAD4 exome AF: 0.000106 AC: 155AN: 1459410Hom.: 0 Cov.: 32 AF XY: 0.0000923 AC XY: 67AN XY: 726060
GnomAD4 genome AF: 0.000131 AC: 20AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74334
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 12, 2024 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 187 of the RBP4 protein (p.Val187Ile). This variant is present in population databases (rs779604024, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with RBP4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1013571). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at