rs1475977

Variant names:

• chr4-2953418-T-C
• rs1475977
• NM_001291978.2:c.747+93A>G

Variant summary

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

The NM_001291978.2(NOP14):​c.747+93A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,396,242 control chromosomes in the GnomAD database, including 116,713 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 0.46 (17452 hom., cov: 33)
  • Exomes 𝑓: 0.39 (99261 hom.)
• Consequence: NOP14 NM_001291978.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 4 publications found

Genes affected

NOP14 (HGNC:16821): (NOP14 nucleolar protein) This gene encodes a protein that plays a role in pre-18s rRNA processing and small ribosomal subunit assembly. The encoded protein may be involved in the regulation of pancreatic cancer cell proliferation and migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

NOP14-AS1 (HGNC:20205): (NOP14 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291978.2. 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
	NOP14	NM_001291978.2	MANE Select	c.747+93A>G		intron	N/A	NP_001278907.1	P78316-1
	NOP14	NM_003703.3		c.747+93A>G		intron	N/A	NP_003694.1	P78316-1
	NOP14	NM_001291979.2		c.747+93A>G		intron	N/A	NP_001278908.1	P78316-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP14	ENST00000416614.7	TSL:1 MANE Select	c.747+93A>G		intron	N/A	ENSP00000405068.2	P78316-1
	NOP14	ENST00000314262.10	TSL:1	c.747+93A>G		intron	N/A	ENSP00000315674.6	P78316-1
	NOP14	ENST00000398071.4	TSL:1	c.747+93A>G		intron	N/A	ENSP00000381146.4	P78316-2

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70271 AN: 152016 Hom.: 17421 Cov.: 33

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.422

GnomAD4 exome AF: 0.392 AC: 487902 AN: 1244108 Hom.: 99261 AF XY: 0.388 AC XY: 240487 AN XY: 619096

African (AFR) AF: 0.629 AC: 17314 AN: 27528

American (AMR) AF: 0.375 AC: 12393 AN: 33076

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 8414 AN: 20788

East Asian (EAS) AF: 0.172 AC: 6541 AN: 38024

South Asian (SAS) AF: 0.243 AC: 17044 AN: 70162

European-Finnish (FIN) AF: 0.525 AC: 26612 AN: 50668

Middle Eastern (MID) AF: 0.405 AC: 1805 AN: 4460

European-Non Finnish (NFE) AF: 0.399 AC: 377636 AN: 947038

Other (OTH) AF: 0.385 AC: 20143 AN: 52364

GnomAD4 genome AF: 0.462 AC: 70356 AN: 152134 Hom.: 17452 Cov.: 33 AF XY: 0.460 AC XY: 34235 AN XY: 74360

African (AFR) AF: 0.631 AC: 26185 AN: 41502

American (AMR) AF: 0.360 AC: 5503 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1393 AN: 3472

East Asian (EAS) AF: 0.180 AC: 935 AN: 5188

South Asian (SAS) AF: 0.245 AC: 1182 AN: 4824

European-Finnish (FIN) AF: 0.544 AC: 5746 AN: 10558

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 28002 AN: 67984

Other (OTH) AF: 0.420 AC: 887 AN: 2114

Alfa AF: 0.460 Hom.: 3347

Bravo AF: 0.458

Asia WGS AF: 0.276 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.50
PhyloP100		-0.042
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1475977;

hg19: chr4-2955145;

COSMIC: COSV58625203;

COSMIC: COSV58625203;