chr5-36952018-C-CTGTGTGTGTGTGTGTG

Position:

• chr5-36952018-C-CTGTGTGTGTGTGTGTG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_133433.4(NIPBL):​c.-79-1579_-79-1564dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.0065 (5 hom., cov: 0)
• Consequence: NIPBL NM_133433.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.326

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-36952018-C-CTGTGTGTGTGTGTGTG is Benign according to our data. Variant chr5-36952018-C-CTGTGTGTGTGTGTGTG is described in ClinVar as [Benign]. Clinvar id is 2655411.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00647 (659/101822) while in subpopulation EAS AF= 0.0128 (33/2576). AF 95% confidence interval is 0.0103. There are 5 homozygotes in gnomad4. There are 311 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 659 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPBL	NM_133433.4	c.-79-1579_-79-1564dup		intron_variant		ENST00000282516.13	NP_597677.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIPBL	ENST00000282516.13	c.-79-1579_-79-1564dup		intron_variant		1	NM_133433.4	ENSP00000282516	P1
NIPBL	ENST00000448238.2	c.-79-1579_-79-1564dup		intron_variant		1		ENSP00000406266
NIPBL	ENST00000652901.1	c.-79-1579_-79-1564dup		intron_variant				ENSP00000499536

Frequencies

GnomAD3 genomes AF: 0.00647 AC: 659 AN: 101800 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.00917

Gnomad AMR AF: 0.00794

Gnomad ASJ AF: 0.00257

Gnomad EAS AF: 0.0128

Gnomad SAS AF: 0.00527

Gnomad FIN AF: 0.000469

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00438

Gnomad OTH AF: 0.00154

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00647 AC: 659 AN: 101822 Hom.: 5 Cov.: 0 AF XY: 0.00652 AC XY: 311 AN XY: 47686

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.00793

Gnomad4 ASJ AF: 0.00257

Gnomad4 EAS AF: 0.0128

Gnomad4 SAS AF: 0.00529

Gnomad4 FIN AF: 0.000469

Gnomad4 NFE AF: 0.00438

Gnomad4 OTH AF: 0.00153

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

NIPBL: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs60067315; hg19: chr5-36952120;