5-36876823-TC-TCC

Variant names:

• chr5-36876823-T-TC
• rs376839773
• NM_133433.4:c.-429dupC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_133433.4(NIPBL):​c.-429dupC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00093 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NIPBL NM_133433.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51

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-DT (HGNC:51293): (NIPBL divergent transcript)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000131 (3/229684) while in subpopulation EAS AF= 0.000141 (3/21280). AF 95% confidence interval is 0.0000383. There are 0 homozygotes in gnomad4_exome. There are 2 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPBL	NM_133433.4	c.-429dupC		5_prime_UTR_variant	Exon 1 of 47	ENST00000282516.13	NP_597677.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPBL	ENST00000282516	c.-429dupC		5_prime_UTR_variant	Exon 1 of 47	1	NM_133433.4	ENSP00000282516.8

Frequencies

GnomAD3 genomes AF: 0.00 AC: 115 AN: 123356 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.000961

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000869

Gnomad ASJ AF: 0.00100

Gnomad EAS AF: 0.00123

Gnomad SAS AF: 0.000269

Gnomad FIN AF: 0.000122

Gnomad MID AF: 0.00373

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.00184

GnomAD4 exome AF: 0.0000131 AC: 3 AN: 229684 Hom.: 0 Cov.: 0 AF XY: 0.0000171 AC XY: 2 AN XY: 117056

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000141

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000932 AC: 115 AN: 123422 Hom.: 0 Cov.: 31 AF XY: 0.000904 AC XY: 54 AN XY: 59724

Gnomad4 AFR AF: 0.000959

Gnomad4 AMR AF: 0.000869

Gnomad4 ASJ AF: 0.00100

Gnomad4 EAS AF: 0.00123

Gnomad4 SAS AF: 0.000270

Gnomad4 FIN AF: 0.000122

Gnomad4 NFE AF: 0.00104

Gnomad4 OTH AF: 0.00182

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs376839773; hg19: chr5-36876925;