rs587783956
Variant names:
Variant summary
Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS2
The NM_133433.4(NIPBL):c.4674C>T(p.Tyr1558Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,630 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 Benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
NIPBL
NM_133433.4 synonymous
NM_133433.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.61
Publications
0 publications found
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]
NIPBL Gene-Disease associations (from GenCC):
- Cornelia de Lange syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- Cornelia de Lange syndrome 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 5-37016068-C-T is Benign according to our data. Variant chr5-37016068-C-T is described in ClinVar as Benign. ClinVar VariationId is 159125.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.61 with no splicing effect.
BS2
High AC in GnomAdExome4 at 5 AD gene.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_133433.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NIPBL | NM_133433.4 | MANE Select | c.4674C>T | p.Tyr1558Tyr | synonymous | Exon 23 of 47 | NP_597677.2 | ||
| NIPBL | NM_001438586.1 | c.4674C>T | p.Tyr1558Tyr | synonymous | Exon 23 of 47 | NP_001425515.1 | |||
| NIPBL | NM_015384.5 | c.4674C>T | p.Tyr1558Tyr | synonymous | Exon 23 of 46 | NP_056199.2 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NIPBL | ENST00000282516.13 | TSL:1 MANE Select | c.4674C>T | p.Tyr1558Tyr | synonymous | Exon 23 of 47 | ENSP00000282516.8 | ||
| NIPBL | ENST00000448238.2 | TSL:1 | c.4674C>T | p.Tyr1558Tyr | synonymous | Exon 23 of 46 | ENSP00000406266.2 | ||
| NIPBL | ENST00000652901.1 | c.4674C>T | p.Tyr1558Tyr | synonymous | Exon 23 of 46 | ENSP00000499536.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251406 AF XY: 0.00000736 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251406
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461630Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727116 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1461630
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
727116
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33468
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26122
East Asian (EAS)
AF:
AC:
0
AN:
39628
South Asian (SAS)
AF:
AC:
0
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
53410
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1111888
Other (OTH)
AF:
AC:
1
AN:
60378
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.515
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
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ClinVar
ClinVar submissions as Germline
Significance:Benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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