chr10-93593863-C-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM1BP4_ModerateBS1_SupportingBS2
The NM_006744.4(RBP4):c.528G>T(p.Glu176Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000373 in 1,612,592 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
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.528G>T | p.Glu176Asp | missense_variant | 5/6 | ENST00000371464.8 | |
RBP4 | NM_001323517.1 | c.528G>T | p.Glu176Asp | missense_variant | 5/6 | ||
RBP4 | NM_001323518.2 | c.522G>T | p.Glu174Asp | missense_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBP4 | ENST00000371464.8 | c.528G>T | p.Glu176Asp | missense_variant | 5/6 | 1 | NM_006744.4 | P1 | |
RBP4 | ENST00000371467.5 | c.528G>T | p.Glu176Asp | missense_variant | 5/6 | 5 | P1 | ||
RBP4 | ENST00000371469.2 | c.522G>T | p.Glu174Asp | missense_variant | 5/6 | 5 | |||
FFAR4 | ENST00000604414.1 | c.697-10211C>A | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000184 AC: 28AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000287 AC: 72AN: 251128Hom.: 0 AF XY: 0.000302 AC XY: 41AN XY: 135746
GnomAD4 exome AF: 0.000392 AC: 573AN: 1460392Hom.: 2 Cov.: 32 AF XY: 0.000391 AC XY: 284AN XY: 726504
GnomAD4 genome AF: 0.000184 AC: 28AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74354
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 18, 2022 | The c.528G>T (p.E176D) alteration is located in exon 5 (coding exon 4) of the RBP4 gene. This alteration results from a G to T substitution at nucleotide position 528, causing the glutamic acid (E) at amino acid position 176 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 176 of the RBP4 protein (p.Glu176Asp). This variant is present in population databases (rs150540008, gnomAD 0.05%). 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: 943659). 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