rs587783962

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_133433.4(NIPBL):​c.5211G>A​(p.Gln1737Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,386 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: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NIPBL
NM_133433.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.62

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 -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 5-37020659-G-A is Benign according to our data. Variant chr5-37020659-G-A is described in ClinVar as Benign. ClinVar VariationId is 159136.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.62 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.00000205 (3/1461386) while in subpopulation AFR AF = 0.0000896 (3/33476). AF 95% confidence interval is 0.0000238. There are 0 homozygotes in GnomAdExome4. There are 0 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

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
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
NIPBL
NM_133433.4
MANE Select
c.5211G>Ap.Gln1737Gln
synonymous
Exon 26 of 47NP_597677.2
NIPBL
NM_001438586.1
c.5211G>Ap.Gln1737Gln
synonymous
Exon 26 of 47NP_001425515.1
NIPBL
NM_015384.5
c.5211G>Ap.Gln1737Gln
synonymous
Exon 26 of 46NP_056199.2

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
NIPBL
ENST00000282516.13
TSL:1 MANE Select
c.5211G>Ap.Gln1737Gln
synonymous
Exon 26 of 47ENSP00000282516.8
NIPBL
ENST00000448238.2
TSL:1
c.5211G>Ap.Gln1737Gln
synonymous
Exon 26 of 46ENSP00000406266.2
NIPBL
ENST00000652901.1
c.5211G>Ap.Gln1737Gln
synonymous
Exon 26 of 46ENSP00000499536.1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000796
AC:
2
AN:
251240
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461386
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727028
show subpopulations
African (AFR)
AF:
0.0000896
AC:
3
AN:
33476
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39670
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53322
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111666
Other (OTH)
AF:
0.00
AC:
0
AN:
60376
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome 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
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

ClinVar submissions as Germline

Significance:Benign
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
-
1
not specified (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
CADD
Benign
8.1
DANN
Benign
0.63
PhyloP100
1.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs587783962; hg19: chr5-37020761; API