rs1478785

Variant names:

• chr17-75226770-G-A
• rs1478785
• NM_024844.5:c.1094+613G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 17

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024844.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP85	NM_024844.5	MANE Select	c.1094+613G>A		intron	N/A	NP_079120.1
	NUP85	NM_001330472.2		c.959+613G>A		intron	N/A	NP_001317401.1
	NUP85	NM_001303276.2		c.956+613G>A		intron	N/A	NP_001290205.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP85	ENST00000245544.9	TSL:1 MANE Select	c.1094+613G>A		intron	N/A	ENSP00000245544.4
	NUP85	ENST00000968072.1		c.1094+613G>A		intron	N/A	ENSP00000638131.1
	NUP85	ENST00000898366.1		c.1094+613G>A		intron	N/A	ENSP00000568425.1

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

GnomAD2 exomes AF: 0.750 AC: 90875 AN: 121106 AF XY: 0.758

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 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

African (AFR) AF: 0.142 AC: 1196 AN: 8432

American (AMR) AF: 0.778 AC: 20107 AN: 25832

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 7460 AN: 10284

East Asian (EAS) AF: 0.870 AC: 7654 AN: 8800

South Asian (SAS) AF: 0.803 AC: 46615 AN: 58078

European-Finnish (FIN) AF: 0.843 AC: 9951 AN: 11808

Middle Eastern (MID) AF: 0.657 AC: 1794 AN: 2732

European-Non Finnish (NFE) AF: 0.773 AC: 119086 AN: 154076

Other (OTH) AF: 0.734 AC: 10085 AN: 13744

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

African (AFR) AF: 0.159 AC: 6593 AN: 41452

American (AMR) AF: 0.703 AC: 10735 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2502 AN: 3470

East Asian (EAS) AF: 0.866 AC: 4481 AN: 5174

South Asian (SAS) AF: 0.800 AC: 3848 AN: 4812

European-Finnish (FIN) AF: 0.848 AC: 8998 AN: 10614

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.772 AC: 52463 AN: 67984

Other (OTH) AF: 0.619 AC: 1302 AN: 2102

Alfa AF: 0.745 Hom.: 52441

Bravo AF: 0.577

Asia WGS AF: 0.764 AC: 2660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	12
DANN	Benign	0.62
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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