rs1478785

Positions:

• chr17-75226770-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024844.5(NUP85):​c.1094+613G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 445,868 control chromosomes in the GnomAD database, including 121,401 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 0.60 (33682 hom., cov: 31)
  • Exomes 𝑓: 0.76 (87719 hom.)
• Consequence: NUP85 NM_024844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

Genes affected

NUP85 (HGNC:8734): (nucleoporin 85) This gene encodes a protein component of the Nup107-160 subunit of the nuclear pore complex. Nuclear pore complexes are embedded in the nuclear envelope and promote bidirectional transport of macromolecules between the cytoplasm and nucleus. The encoded protein can also bind to the C-terminus of chemokine (C-C motif) receptor 2 (CCR2) and promote chemotaxis of monocytes, thereby participating in the inflammatory response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

NUP85 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP85	NM_024844.5	c.1094+613G>A		intron_variant		ENST00000245544.9	NP_079120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP85	ENST00000245544.9	c.1094+613G>A		intron_variant		1	NM_024844.5	ENSP00000245544.4

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91859 AN: 151966 Hom.: 33673 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.617

GnomAD3 exomes AF: 0.750 AC: 90875 AN: 121106 Hom.: 35606 AF XY: 0.758 AC XY: 50374 AN XY: 66440

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.776

Gnomad ASJ exome AF: 0.724

Gnomad EAS exome AF: 0.864

Gnomad SAS exome AF: 0.803

Gnomad FIN exome AF: 0.839

Gnomad NFE exome AF: 0.766

Gnomad OTH exome AF: 0.751

GnomAD4 exome AF: 0.762 AC: 223948 AN: 293786 Hom.: 87719 Cov.: 0 AF XY: 0.770 AC XY: 129338 AN XY: 167970

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.778

Gnomad4 ASJ exome AF: 0.725

Gnomad4 EAS exome AF: 0.870

Gnomad4 SAS exome AF: 0.803

Gnomad4 FIN exome AF: 0.843

Gnomad4 NFE exome AF: 0.773

Gnomad4 OTH exome AF: 0.734

GnomAD4 genome AF: 0.604 AC: 91875 AN: 152082 Hom.: 33682 Cov.: 31 AF XY: 0.614 AC XY: 45664 AN XY: 74358

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.619

Alfa AF: 0.742 Hom.: 28731

Bravo AF: 0.577

Asia WGS AF: 0.764 AC: 2660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	12
DANN	Benign	0.62

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: rs1478785; hg19: chr17-73222865; COSMIC: COSV55466505; COSMIC: COSV55466505;