rs757731487
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_133433.4(NIPBL):c.6955-12_6955-9del 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 0.000000906 in 1,103,392 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 9.1e-7 ( 0 hom. )
Consequence
NIPBL
NM_133433.4 splice_polypyrimidine_tract, intron
NM_133433.4 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.98
Genes affected
NIPBL (HGNC:28862): (NIPBL cohesin loading factor) This gene encodes the homolog of the Drosophila melanogaster Nipped-B gene product and fungal Scc2-type sister chromatid cohesion proteins. The Drosophila protein facilitates enhancer-promoter communication of remote enhancers and plays a role in developmental regulation. It is also homologous to a family of chromosomal adherins with broad roles in sister chromatid cohesion, chromosome condensation, and DNA repair. The human protein has a bipartite nuclear targeting sequence and a putative HEAT repeat. Condensins, cohesins and other complexes with chromosome-related functions also contain HEAT repeats. Mutations in this gene result in Cornelia de Lange syndrome, a disorder characterized by dysmorphic facial features, growth delay, limb reduction defects, and cognitive disability. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NIPBL | NM_133433.4 | c.6955-12_6955-9del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000282516.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NIPBL | ENST00000282516.13 | c.6955-12_6955-9del | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_133433.4 | P1 | |||
NIPBL | ENST00000448238.2 | c.6955-12_6955-9del | splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
NIPBL | ENST00000652901.1 | c.6955-12_6955-9del | splice_polypyrimidine_tract_variant, intron_variant | ||||||
NIPBL | ENST00000514335.1 | n.825_828del | non_coding_transcript_exon_variant | 1/7 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 9.06e-7 AC: 1AN: 1103392Hom.: 0 AF XY: 0.00000181 AC XY: 1AN XY: 552566
GnomAD4 exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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32
Bravo
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ClinVar
Not reported inComputational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at