rs1356246775
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_133433.4(NIPBL):āc.4203A>Gā(p.Leu1401=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,611,692 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 (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 6.9e-7 ( 0 hom. )
Consequence
NIPBL
NM_133433.4 synonymous
NM_133433.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.232
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 5-37007438-A-G is Benign according to our data. Variant chr5-37007438-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 476589.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.232 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NIPBL | NM_133433.4 | c.4203A>G | p.Leu1401= | synonymous_variant | 18/47 | ENST00000282516.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NIPBL | ENST00000282516.13 | c.4203A>G | p.Leu1401= | synonymous_variant | 18/47 | 1 | NM_133433.4 | P1 | |
NIPBL | ENST00000448238.2 | c.4203A>G | p.Leu1401= | synonymous_variant | 18/46 | 1 | |||
NIPBL | ENST00000652901.1 | c.4203A>G | p.Leu1401= | synonymous_variant | 18/46 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152018Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459674Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726272
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152018Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74234
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cornelia de Lange syndrome 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 14, 2022 | - - |
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