GeneBe

rs60067315

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_133433.4(NIPBL):​c.-79-1585_-79-1564delTGTGTGTGTGTGTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 0)

Consequence

NIPBL
NM_133433.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.326

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: Benign. The variant received -8 ACMG points.

BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000167 (17/101936) while in subpopulation NFE AF = 0.000246 (13/52756). AF 95% confidence interval is 0.000145. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
BS2
High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NIPBLNM_133433.4 linkc.-79-1585_-79-1564delTGTGTGTGTGTGTGTGTGTGTG intron_variant Intron 1 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.-79-1599_-79-1578delTGTGTGTGTGTGTGTGTGTGTG intron_variant Intron 1 of 46 1 NM_133433.4 ENSP00000282516.8 Q6KC79-1
NIPBLENST00000448238.2 linkc.-79-1599_-79-1578delTGTGTGTGTGTGTGTGTGTGTG intron_variant Intron 1 of 45 1 ENSP00000406266.2 Q6KC79-2
NIPBLENST00000652901.1 linkc.-79-1599_-79-1578delTGTGTGTGTGTGTGTGTGTGTG intron_variant Intron 1 of 45 ENSP00000499536.1 A0A590UJS4

Frequencies

GnomAD3 genomes
AF:
0.000167
AC:
17
AN:
101936
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000955
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000703
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000246
Gnomad OTH
AF:
0.00
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.000167
AC:
17
AN:
101936
Hom.:
0
Cov.:
0
AF XY:
0.0000838
AC XY:
4
AN XY:
47718
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
24908
American (AMR)
AF:
0.0000955
AC:
1
AN:
10468
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2728
East Asian (EAS)
AF:
0.00
AC:
0
AN:
2592
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2088
European-Finnish (FIN)
AF:
0.000703
AC:
3
AN:
4268
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
178
European-Non Finnish (NFE)
AF:
0.000246
AC:
13
AN:
52756
Other (OTH)
AF:
0.00
AC:
0
AN:
1296
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.604
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.33

Splicing

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

Publications

Other links and lift over

dbSNP: rs60067315; hg19: chr5-36952120; API