rs797045759
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_133433.4(NIPBL):c.4422-12del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,581,336 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 7 hom. )
Consequence
NIPBL
NM_133433.4 intron
NM_133433.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.32
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 Benign. Variant got -16 ACMG points.
BP6
?
Variant 5-37010067-AT-A is Benign according to our data. Variant chr5-37010067-AT-A is described in ClinVar as [Benign]. Clinvar id is 211635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-37010067-AT-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00102 (155/152162) while in subpopulation NFE AF= 0.0016 (109/67990). AF 95% confidence interval is 0.00136. There are 0 homozygotes in gnomad4. There are 72 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 155 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NIPBL | NM_133433.4 | c.4422-12del | intron_variant | ENST00000282516.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NIPBL | ENST00000282516.13 | c.4422-12del | intron_variant | 1 | NM_133433.4 | P1 | |||
NIPBL | ENST00000448238.2 | c.4422-12del | intron_variant | 1 | |||||
NIPBL | ENST00000652901.1 | c.4422-12del | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00102 AC: 155AN: 152044Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00142 AC: 354AN: 249898Hom.: 2 AF XY: 0.00155 AC XY: 209AN XY: 135138
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GnomAD4 exome AF: 0.00149 AC: 2133AN: 1429174Hom.: 7 Cov.: 27 AF XY: 0.00146 AC XY: 1038AN XY: 713356
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GnomAD4 genome ? AF: 0.00102 AC: 155AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.000968 AC XY: 72AN XY: 74388
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Cornelia de Lange syndrome 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2020 | - - |
Computational 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