rs149115930
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_133433.4(NIPBL):c.3768+34T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000238 in 1,176,060 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
NIPBL
NM_133433.4 intron
NM_133433.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.37
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 5-37002799-T-G is Benign according to our data. Variant chr5-37002799-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 436011.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NIPBL | NM_133433.4 | c.3768+34T>G | intron_variant | ENST00000282516.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NIPBL | ENST00000282516.13 | c.3768+34T>G | intron_variant | 1 | NM_133433.4 | P1 | |||
NIPBL | ENST00000448238.2 | c.3768+34T>G | intron_variant | 1 | |||||
NIPBL | ENST00000652901.1 | c.3768+34T>G | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152112Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000517 AC: 12AN: 232174Hom.: 0 AF XY: 0.0000476 AC XY: 6AN XY: 126114
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GnomAD4 exome AF: 0.0000225 AC: 23AN: 1023830Hom.: 0 Cov.: 14 AF XY: 0.0000190 AC XY: 10AN XY: 527496
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74438
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 22, 2016 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at