17-81624787-C-T

Variant names:

• chr17-81624787-C-T
• rs7219915
• NM_017921.4:c.97-2509G>A

Variant summary

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

The NM_017921.4(NPLOC4):​c.97-2509G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,984 control chromosomes in the GnomAD database, including 30,871 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 0.62 (30871 hom., cov: 32)
• Consequence: NPLOC4 NM_017921.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• Publications: 12 publications found

Genes affected

NPLOC4 (HGNC:18261): (NPL4 homolog, ubiquitin recognition factor) Predicted to enable ATPase binding activity; ubiquitin binding activity; and ubiquitin protein ligase binding activity. Predicted to contribute to K48-linked polyubiquitin modification-dependent protein binding activity and K63-linked polyubiquitin modification-dependent protein binding activity. Involved in negative regulation of RIG-I signaling pathway; negative regulation of type I interferon production; and proteolysis involved in cellular protein catabolic process. Located in nucleus. Part of UFD1-NPL4 complex and VCP-NPL4-UFD1 AAA ATPase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017921.4. 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
	NPLOC4	NM_017921.4	MANE Select	c.97-2509G>A		intron	N/A	NP_060391.2	Q8TAT6-1
	NPLOC4	NM_001437986.1		c.97-2509G>A		intron	N/A	NP_001424915.1
	NPLOC4	NM_001369698.1		c.97-2509G>A		intron	N/A	NP_001356627.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPLOC4	ENST00000331134.11	TSL:1 MANE Select	c.97-2509G>A		intron	N/A	ENSP00000331487.5	Q8TAT6-1
	NPLOC4	ENST00000705719.1		c.226-2509G>A		intron	N/A	ENSP00000516165.1	A0A994J7H4
	NPLOC4	ENST00000374747.9	TSL:2	c.97-2509G>A		intron	N/A	ENSP00000363879.5	Q8TAT6-2

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93506 AN: 151866 Hom.: 30800 Cov.: 32

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.616 AC: 93636 AN: 151984 Hom.: 30871 Cov.: 32 AF XY: 0.616 AC XY: 45758 AN XY: 74276

African (AFR) AF: 0.806 AC: 33429 AN: 41482

American (AMR) AF: 0.663 AC: 10125 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1856 AN: 3468

East Asian (EAS) AF: 0.994 AC: 5128 AN: 5158

South Asian (SAS) AF: 0.711 AC: 3428 AN: 4822

European-Finnish (FIN) AF: 0.443 AC: 4672 AN: 10554

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.487 AC: 33051 AN: 67920

Other (OTH) AF: 0.595 AC: 1256 AN: 2112

Alfa AF: 0.529 Hom.: 12701

Bravo AF: 0.645

Asia WGS AF: 0.874 AC: 3040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.62
PhyloP100		-0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7219915; hg19: chr17-79591813;