rs11549936
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000709.4(BCKDHA):c.116C>A(p.Pro39His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,614,072 control chromosomes in the GnomAD database, including 13,304 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P39R) has been classified as Likely benign.
Frequency
Consequence
NM_000709.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCKDHA | NM_000709.4 | c.116C>A | p.Pro39His | missense_variant | 2/9 | ENST00000269980.7 | |
BCKDHA | NM_001164783.2 | c.116C>A | p.Pro39His | missense_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCKDHA | ENST00000269980.7 | c.116C>A | p.Pro39His | missense_variant | 2/9 | 1 | NM_000709.4 | P1 | |
BCKDHA | ENST00000542943.5 | c.116C>A | p.Pro39His | missense_variant | 2/7 | 5 | |||
BCKDHA | ENST00000457836.6 | c.58-8C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 2 | |||||
BCKDHA | ENST00000538423.5 | n.136C>A | non_coding_transcript_exon_variant | 2/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0890 AC: 13543AN: 152128Hom.: 765 Cov.: 32
GnomAD3 exomes AF: 0.0988 AC: 24826AN: 251376Hom.: 1490 AF XY: 0.104 AC XY: 14106AN XY: 135886
GnomAD4 exome AF: 0.125 AC: 183247AN: 1461826Hom.: 12540 Cov.: 34 AF XY: 0.126 AC XY: 91343AN XY: 727218
GnomAD4 genome ? AF: 0.0889 AC: 13541AN: 152246Hom.: 764 Cov.: 32 AF XY: 0.0861 AC XY: 6409AN XY: 74434
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 17, 2013 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Maple syrup urine disease Benign:3
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 08, 2017 | Variant summary: The BCKDHA c.116C>A (p.Pro39His) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 11936/121154 control chromosomes (711 homozygotes) at a frequency of 0.0985192, which is approximately 59 times the estimated maximal expected allele frequency of a pathogenic BCKDHA variant (0.0016771), suggesting this variant is likely a benign polymorphism. This variant has been reported in multiple affected individuals who also carried other variants in BCKDHB that can explain the phenotype, and authors interpreted the variant of interest as silent variant. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign. - |
Maple syrup urine disease type 1A Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at