rs4502885
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_183050.4(BCKDHB):c.*994G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,096 control chromosomes in the GnomAD database, including 46,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.78 ( 46288 hom., cov: 32)
Failed GnomAD Quality Control
Consequence
BCKDHB
NM_183050.4 3_prime_UTR
NM_183050.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.217
Genes affected
BCKDHB (HGNC:987): (branched chain keto acid dehydrogenase E1 subunit beta) This gene encodes the E1 beta subunit of branched-chain keto acid dehydrogenase, which is a multienzyme complex associated with the inner membrane of mitochondria. This enzyme complex functions in the catabolism of branched-chain amino acids. Mutations in this gene have been associated with maple syrup urine disease (MSUD), type 1B, a disease characterized by a maple syrup odor to the urine in addition to mental and physical retardation and feeding problems. Alternative splicing at this locus results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 6-80344798-G-A is Benign according to our data. Variant chr6-80344798-G-A is described in ClinVar as [Benign]. Clinvar id is 358196.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCKDHB | NM_183050.4 | c.*994G>A | 3_prime_UTR_variant | 10/10 | ENST00000320393.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCKDHB | ENST00000320393.9 | c.*994G>A | 3_prime_UTR_variant | 10/10 | 1 | NM_183050.4 | P1 | ||
BCKDHB | ENST00000356489.9 | c.*8+986G>A | intron_variant | 1 | P1 | ||||
BCKDHB | ENST00000491328.1 | n.242+986G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.777 AC: 118129AN: 151978Hom.: 46262 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0AC: 0AN: 0Hom.: 0 Cov.: 0AC XY: 0AN XY: 0
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GnomAD4 genome ? AF: 0.777 AC: 118212AN: 152096Hom.: 46288 Cov.: 32 AF XY: 0.775 AC XY: 57615AN XY: 74340
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Maple syrup urine disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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