rs13189047

Positions:

• chr5-178151874-C-A
• chr5-178151874-C-T

Variant summary

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

The ENST00000274606.8(NHP2):​c.231-881G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,890 control chromosomes in the GnomAD database, including 5,321 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 0.25 (5321 hom., cov: 32)
• Consequence: NHP2 ENST00000274606.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

Genes affected

NHP2 (HGNC:14377): (NHP2 ribonucleoprotein) This gene is a member of the H/ACA snoRNPs (small nucleolar ribonucleoproteins) gene family. snoRNPs are involved in various aspects of rRNA processing and modification and have been classified into two families: C/D and H/ACA. The H/ACA snoRNPs also include the DKC1, NOLA1 and NOLA3 proteins. These four H/ACA snoRNP proteins localize to the dense fibrillar components of nucleoli and to coiled (Cajal) bodies in the nucleus. Both 18S rRNA production and rRNA pseudouridylation are impaired if any one of the four proteins is depleted. The four H/ACA snoRNP proteins are also components of the telomerase complex. This gene encodes a protein related to Saccharomyces cerevisiae Nhp2p. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHP2	NM_017838.4	c.231-881G>T		intron_variant		ENST00000274606.8	NP_060308.1
NHP2	NM_001034833.2	c.230+1617G>T		intron_variant			NP_001030005.1
NHP2	NM_001396110.1	c.231-881G>T		intron_variant			NP_001383039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHP2	ENST00000274606.8	c.231-881G>T		intron_variant		1	NM_017838.4	ENSP00000274606	P1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37806 AN: 151772 Hom.: 5319 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.249 AC: 37844 AN: 151890 Hom.: 5321 Cov.: 32 AF XY: 0.246 AC XY: 18251 AN XY: 74246

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.257

Alfa AF: 0.183 Hom.: 1218

Bravo AF: 0.261

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.92
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13189047; hg19: chr5-177578875; COSMIC: COSV51071005; COSMIC: COSV51071005;