rs78827246

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_133433.4(NIPBL):c.3575-17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,599,282 control chromosomes in the GnomAD database, including 11,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1223 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10750 hom. )

Consequence

NIPBL
NM_133433.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.330

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 5-37000972-A-G is Benign according to our data. Variant chr5-37000972-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 96340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-37000972-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPBL	NM_133433.4 link	c.3575-17A>G		intron_variant	Intron 13 of 46	ENST00000282516.13	NP_597677.2	Q6KC79-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NIPBL	ENST00000282516.13 link	c.3575-17A>G	intron_variant	Intron 13 of 46	1	NM_133433.4	ENSP00000282516.8	Q6KC79-1
NIPBL	ENST00000448238.2 link	c.3575-17A>G	intron_variant	Intron 13 of 45	1		ENSP00000406266.2	Q6KC79-2
NIPBL	ENST00000652901.1 link	c.3575-17A>G	intron_variant	Intron 13 of 45			ENSP00000499536.1	A0A590UJS4

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18561

AN:

152064

Hom.:

1220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0980

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.148

GnomAD3 exomes

AF:

0.137

AC:

34357

AN:

250380

Hom.:

2591

AF XY:

0.132

AC XY:

17927

AN XY:

135456

show subpopulations

Gnomad AFR exome

AF:

0.0929

Gnomad AMR exome

AF:

0.234

Gnomad ASJ exome

AF:

0.205

Gnomad EAS exome

AF:

0.129

Gnomad SAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.118

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.118

AC:

170917

AN:

1447100

Hom.:

10750

Cov.:

AF XY:

0.118

AC XY:

85003

AN XY:

720944

show subpopulations

Gnomad4 AFR exome

AF:

0.0979

Gnomad4 AMR exome

AF:

0.227

Gnomad4 ASJ exome

AF:

0.202

Gnomad4 EAS exome

AF:

0.108

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.112

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.122

AC:

18588

AN:

152182

Hom.:

1223

Cov.:

AF XY:

0.125

AC XY:

9313

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0980

Gnomad4 AMR

AF:

0.189

Gnomad4 ASJ

AF:

0.194

Gnomad4 EAS

AF:

0.130

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.153

Alfa

AF:

0.134

Hom.:

249

Bravo

AF:

0.126

Asia WGS

AF:

0.170

AC:

590

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 02, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cornelia de Lange syndrome 1

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

DANN

Benign

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over