rs1475977

Positions:

• chr4-2953418-T-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOP14	NM_001291978.2	c.747+93A>G		intron_variant		ENST00000416614.7	NP_001278907.1
NOP14	NM_003703.3	c.747+93A>G		intron_variant			NP_003694.1
NOP14	NM_001291979.2	c.747+93A>G		intron_variant			NP_001278908.1
NOP14	XM_047416338.1	c.747+93A>G		intron_variant			XP_047272294.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOP14	ENST00000416614.7	c.747+93A>G		intron_variant		1	NM_001291978.2	ENSP00000405068.2

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

Gnomad4 AFR exome AF: 0.629

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.405

Gnomad4 EAS exome AF: 0.172

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.525

Gnomad4 NFE exome AF: 0.399

Gnomad4 OTH exome AF: 0.385

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

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.420

Alfa AF: 0.455 Hom.: 3184

Bravo AF: 0.458

Asia WGS AF: 0.276 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs1475977; hg19: chr4-2955145; COSMIC: COSV58625203; COSMIC: COSV58625203;