rs9448894
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_183050.4(BCKDHB):c.197-11G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,413,562 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 Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
BCKDHB
NM_183050.4 splice_polypyrimidine_tract, intron
NM_183050.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00006989
2
Clinical Significance
Conservation
PhyloP100: -0.218
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 Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 6-80127536-G-A is Benign according to our data. Variant chr6-80127536-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2889200.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCKDHB | NM_183050.4 | c.197-11G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000320393.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCKDHB | ENST00000320393.9 | c.197-11G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_183050.4 | P1 | |||
BCKDHB | ENST00000356489.9 | c.197-11G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | P1 | ||||
BCKDHB | ENST00000369760.8 | c.197-11G>A | splice_polypyrimidine_tract_variant, intron_variant | 3 | |||||
BCKDHB | ENST00000486968.1 | n.111-11G>A | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000426 AC: 1AN: 234524Hom.: 0 AF XY: 0.00000789 AC XY: 1AN XY: 126796
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GnomAD4 exome AF: 0.00000283 AC: 4AN: 1413562Hom.: 0 Cov.: 31 AF XY: 0.00000284 AC XY: 2AN XY: 703310
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GnomAD4 genome ? Cov.: 32
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Cov.:
32
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Maple syrup urine disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at