chr15-40217602-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_001211.6(BUB1B):c.2785G>A(p.Gly929Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000083 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G929V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001211.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BUB1B | NM_001211.6 | c.2785G>A | p.Gly929Ser | missense_variant | 21/23 | ENST00000287598.11 | |
BUB1B-PAK6 | NM_001128628.3 | c.-266G>A | 5_prime_UTR_variant | 1/11 | |||
LOC107984763 | XR_001751506.2 | n.217+21883C>T | intron_variant, non_coding_transcript_variant | ||||
BUB1B-PAK6 | NM_001128629.3 | c.-183G>A | 5_prime_UTR_variant | 1/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BUB1B | ENST00000287598.11 | c.2785G>A | p.Gly929Ser | missense_variant | 21/23 | 1 | NM_001211.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000441 AC: 67AN: 152092Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000191 AC: 48AN: 251426Hom.: 0 AF XY: 0.000132 AC XY: 18AN XY: 135898
GnomAD4 exome AF: 0.0000458 AC: 67AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.0000523 AC XY: 38AN XY: 727240
GnomAD4 genome AF: 0.000440 AC: 67AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74414
ClinVar
Submissions by phenotype
Microcephaly Uncertain:1
Uncertain significance, no assertion criteria provided | research | Department of Pediatrics, Samsung Medical Center, Samsung Medical Center | - | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 29, 2018 | - - |
Mosaic variegated aneuploidy syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 20, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 929 of the BUB1B protein (p.Gly929Ser). This variant is present in population databases (rs143232848, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with BUB1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 403742). 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 disruptive. 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 15, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at