5-37036347-GTATATATATATA-GTATATATATATATATA

Variant names:

• chr5-37036347-G-GTATA
• rs10554564
• NM_133433.4:c.5863-14_5863-11dupATAT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_133433.4(NIPBL):​c.5863-14_5863-11dupATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (208 hom., cov: 0)
  • Exomes 𝑓: 0.0019 (3 hom.)
• Consequence: NIPBL NM_133433.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0120

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 -16 ACMG points.

• BP6: Variant 5-37036347-G-GTATA is Benign according to our data. Variant chr5-37036347-G-GTATA is described in ClinVar as [Benign]. Clinvar id is 167360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPBL	NM_133433.4	c.5863-14_5863-11dupATAT		intron_variant	Intron 32 of 46	ENST00000282516.13	NP_597677.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPBL	ENST00000282516.13	c.5863-32_5863-31insTATA		intron_variant	Intron 32 of 46	1	NM_133433.4	ENSP00000282516.8
NIPBL	ENST00000448238.2	c.5863-32_5863-31insTATA		intron_variant	Intron 32 of 45	1		ENSP00000406266.2
NIPBL	ENST00000652901.1	c.5863-32_5863-31insTATA		intron_variant	Intron 32 of 45			ENSP00000499536.1

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4182 AN: 135944 Hom.: 206 Cov.: 0

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000211

Gnomad SAS AF: 0.00116

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00345

Gnomad NFE AF: 0.000313

Gnomad OTH AF: 0.0240

GnomAD3 exomes AF: 0.00189 AC: 62 AN: 32888 Hom.: 0 AF XY: 0.00122 AC XY: 24 AN XY: 19604

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.00506

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00173

Gnomad FIN exome AF: 0.000135

Gnomad NFE exome AF: 0.000535

Gnomad OTH exome AF: 0.00157

GnomAD4 exome AF: 0.00194 AC: 482 AN: 248048 Hom.: 3 Cov.: 0 AF XY: 0.00176 AC XY: 238 AN XY: 135454

Gnomad4 AFR exome AF: 0.0607

Gnomad4 AMR exome AF: 0.00635

Gnomad4 ASJ exome AF: 0.000150

Gnomad4 EAS exome AF: 0.000513

Gnomad4 SAS exome AF: 0.00156

Gnomad4 FIN exome AF: 0.000286

Gnomad4 NFE exome AF: 0.000547

Gnomad4 OTH exome AF: 0.00529

GnomAD4 genome AF: 0.0308 AC: 4184 AN: 135938 Hom.: 208 Cov.: 0 AF XY: 0.0302 AC XY: 1968 AN XY: 65236

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0129

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000212

Gnomad4 SAS AF: 0.00117

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000313

Gnomad4 OTH AF: 0.0239

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jan 10, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Dec 22, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: rs10554564; hg19: chr5-37036449;