Genetic Variant NIPBL:c.6955-12_6955-9delTTTT (chr5-37051759-ATTTT-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_133433.4(NIPBL):c.6955-12_6955-9delTTTT 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

NIPBL links:

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
NIPBL	NM_133433.4 link	c.6955-12_6955-9delTTTT		intron_variant	Intron 40 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.6955-12_6955-9delTTTT	intron_variant	Intron 40 of 46	1	NM_133433.4	ENSP00000282516.8	Q6KC79-1
NIPBL	ENST00000448238.2 link	c.6955-12_6955-9delTTTT	intron_variant	Intron 40 of 45	1		ENSP00000406266.2	Q6KC79-2
NIPBL	ENST00000514335.1 link	n.825_828delTTTT	non_coding_transcript_exon_variant	Exon 1 of 7	2
NIPBL	ENST00000652901.1 link	c.6955-12_6955-9delTTTT	intron_variant	Intron 40 of 45			ENSP00000499536.1	A0A590UJS4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.06e-7

AC:

AN:

1103392

Hom.:

AF XY:

0.00000181

AC XY:

AN XY:

552566

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25220

American (AMR)

AF:

0.00

AC:

AN:

35450

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19762

East Asian (EAS)

AF:

0.00

AC:

AN:

30226

South Asian (SAS)

AF:

0.00

AC:

AN:

67284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43954

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4744

European-Non Finnish (NFE)

AF:

0.00000120

AC:

AN:

831198

Other (OTH)

AF:

0.00

AC:

AN:

45554

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

5-37051759-ATTTTT-AT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over