GeneBe

rs757731487

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_133433.4(NIPBL):​c.6955-13_6955-9delTTTTT variant causes a 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 9.1e-7 ( 0 hom. )

Consequence

NIPBL
NM_133433.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.98

Publications

0 publications found
Variant links:
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 syndrome
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
  • Cornelia de Lange syndrome 1
    Inheritance: 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: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NIPBLNM_133433.4 linkc.6955-13_6955-9delTTTTT intron_variant Intron 40 of 46 ENST00000282516.13 NP_597677.2 Q6KC79-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NIPBLENST00000282516.13 linkc.6955-13_6955-9delTTTTT intron_variant Intron 40 of 46 1 NM_133433.4 ENSP00000282516.8 Q6KC79-1
NIPBLENST00000448238.2 linkc.6955-13_6955-9delTTTTT intron_variant Intron 40 of 45 1 ENSP00000406266.2 Q6KC79-2
NIPBLENST00000514335.1 linkn.824_828delTTTTT non_coding_transcript_exon_variant Exon 1 of 7 2
NIPBLENST00000652901.1 linkc.6955-13_6955-9delTTTTT intron_variant Intron 40 of 45 ENSP00000499536.1 A0A590UJS4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
9.06e-7
AC:
1
AN:
1103392
Hom.:
0
AF XY:
0.00000181
AC XY:
1
AN XY:
552566
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
25220
American (AMR)
AF:
0.00
AC:
0
AN:
35450
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19762
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30226
South Asian (SAS)
AF:
0.00
AC:
0
AN:
67284
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
43954
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4744
European-Non Finnish (NFE)
AF:
0.00000120
AC:
1
AN:
831198
Other (OTH)
AF:
0.00
AC:
0
AN:
45554
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
2.0
La Branchor
0.34
BranchPoint Hunter
4.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs757731487; hg19: chr5-37051861; API