chr2-218660148-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_004328.5(BCS1L):c.-147A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,236 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).
Frequency
Consequence
NM_004328.5 5_prime_UTR
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BCS1L | NM_001079866.2 | c.-50+405A>G | intron_variant | Intron 1 of 7 | ENST00000359273.8 | NP_001073335.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152236Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 0
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74370
ClinVar
Submissions by phenotype
GRACILE syndrome Pathogenic:1Uncertain:1
- -
- -
Mitochondrial complex III deficiency nuclear type 1 Pathogenic:1
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. -
not provided Uncertain:1
This variant occurs in a non-coding region of the BCS1L gene. It does not change the encoded amino acid sequence of the BCS1L protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with mitochondrial complex III deficiency (PMID: 19389488, 28128857, 28496993). ClinVar contains an entry for this variant (Variation ID: 553134). Studies have shown that this variant alters BCS1L gene expression (PMID: 19389488). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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