11-3671890-T-C

Variant names:

• chr11-3671890-T-C
• rs2231532
• ENST00000533346.5:c.245-474A>G

Variant summary

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

The ENST00000533346.5(NUP98):​c.245-474A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,042 control chromosomes in the GnomAD database, including 21,369 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 0.51 (21369 hom., cov: 32)
• Consequence: NUP98 ENST00000533346.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 12 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.689 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.245-474A>G		intron_variant	Intron 2 of 2	2		ENSP00000432275.1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78072 AN: 151924 Hom.: 21356 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.514 AC: 78124 AN: 152042 Hom.: 21369 Cov.: 32 AF XY: 0.513 AC XY: 38151 AN XY: 74302

African (AFR) AF: 0.323 AC: 13407 AN: 41468

American (AMR) AF: 0.700 AC: 10694 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1879 AN: 3472

East Asian (EAS) AF: 0.647 AC: 3336 AN: 5156

South Asian (SAS) AF: 0.477 AC: 2297 AN: 4814

European-Finnish (FIN) AF: 0.503 AC: 5312 AN: 10554

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39323 AN: 67980

Other (OTH) AF: 0.542 AC: 1145 AN: 2112

Alfa AF: 0.559 Hom.: 64250

Bravo AF: 0.527

Asia WGS AF: 0.563 AC: 1957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.60
PhyloP100		1.1
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: rs2231532; hg19: chr11-3693120;