rs6578411

Variant names:

• chr11-3674742-A-G
• rs6578411
• ENST00000533346.5:c.244+1767T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000533346.5(NUP98):​c.244+1767T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0891 in 152,222 control chromosomes in the GnomAD database, including 693 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.089 (693 hom., cov: 32)
• Consequence: NUP98 ENST00000533346.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99
• Publications: 1 publications found

Genes affected

NUP98 (HGNC:8068): (nucleoporin 98 and 96 precursor) Nuclear pore complexes (NPCs) regulate the transport of macromolecules between the nucleus and cytoplasm, and are composed of many polypeptide subunits, many of which belong to the nucleoporin family. This gene belongs to the nucleoporin gene family and encodes a 186 kDa precursor protein that undergoes autoproteolytic cleavage to generate a 98 kDa nucleoporin and 96 kDa nucleoporin. The 98 kDa nucleoporin contains a Gly-Leu-Phe-Gly (GLGF) repeat domain and participates in many cellular processes, including nuclear import, nuclear export, mitotic progression, and regulation of gene expression. The 96 kDa nucleoporin is a scaffold component of the NPC. Proteolytic cleavage is important for targeting of the proteins to the NPC. Translocations between this gene and many other partner genes have been observed in different leukemias. Rearrangements typically result in chimeras with the N-terminal GLGF domain of this gene to the C-terminus of the partner gene. Alternative splicing results in multiple transcript variants encoding different isoforms, at least two of which are proteolytically processed. Some variants lack the region that encodes the 96 kDa nucleoporin. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP98	ENST00000533346.5	c.244+1767T>C		intron_variant	Intron 2 of 2	2		ENSP00000432275.1

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13564 AN: 152104 Hom.: 693 Cov.: 32

Gnomad AFR AF: 0.0592

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0664

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0423

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0830

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0891 AC: 13566 AN: 152222 Hom.: 693 Cov.: 32 AF XY: 0.0881 AC XY: 6557 AN XY: 74424

African (AFR) AF: 0.0591 AC: 2458 AN: 41560

American (AMR) AF: 0.0663 AC: 1013 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3464

East Asian (EAS) AF: 0.0424 AC: 220 AN: 5184

South Asian (SAS) AF: 0.166 AC: 800 AN: 4818

European-Finnish (FIN) AF: 0.0830 AC: 879 AN: 10586

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7175 AN: 68014

Other (OTH) AF: 0.101 AC: 213 AN: 2110

Alfa AF: 0.103 Hom.: 1494

Bravo AF: 0.0839

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.8
DANN	Benign	0.72
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6578411; hg19: chr11-3695972;