rs200384643
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_139343.3(BIN1):c.1462-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000781 in 1,613,594 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_139343.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BIN1 | NM_139343.3 | c.1462-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000316724.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BIN1 | ENST00000316724.10 | c.1462-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_139343.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152196Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000132 AC: 33AN: 250894Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135832
GnomAD4 exome AF: 0.0000773 AC: 113AN: 1461280Hom.: 2 Cov.: 32 AF XY: 0.0000812 AC XY: 59AN XY: 727014
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6AN XY: 74478
ClinVar
Submissions by phenotype
Myopathy, centronuclear, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 28, 2023 | This sequence change falls in intron 16 of the BIN1 gene. It does not directly change the encoded amino acid sequence of the BIN1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs200384643, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with BIN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 577844). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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