rs143017094
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001122955.4(BSCL2):c.1361G>T(p.Arg454Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,812 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 Uncertain significance (★).
Frequency
Consequence
NM_001122955.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BSCL2 | NM_001122955.4 | c.1361G>T | p.Arg454Leu | missense_variant | Exon 11 of 11 | ENST00000360796.10 | NP_001116427.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BSCL2 | ENST00000360796.10 | c.1361G>T | p.Arg454Leu | missense_variant | Exon 11 of 11 | 1 | NM_001122955.4 | ENSP00000354032.5 | ||
HNRNPUL2-BSCL2 | ENST00000403734.2 | n.*1412G>T | non_coding_transcript_exon_variant | Exon 24 of 24 | 2 | ENSP00000456010.1 | ||||
HNRNPUL2-BSCL2 | ENST00000403734.2 | n.*1412G>T | 3_prime_UTR_variant | Exon 24 of 24 | 2 | ENSP00000456010.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461812Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727212
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
A variant of uncertain significance has been identified in the BSCL2 gene. The c.1169 G>T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Several in-silico splice prediction models predict that c.1169 G>T enhances a cryptic acceptor site which may supplant the natural acceptor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. If the c.1169 G>T variant does not affect splicing, it will result in the R390L missense change. The R390L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at