rs13189047

Variant names:

• chr5-178151874-C-A
• rs13189047
• NM_017838.4:c.231-881G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_017838.4(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 NM_017838.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 4 publications found

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]

NHP2 Gene-Disease associations (from GenCC):

• dyskeratosis congenita, autosomal recessive 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• dyskeratosis congenita

  Inheritance: AD, AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017838.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHP2	NM_017838.4	MANE Select	c.231-881G>T		intron	N/A	NP_060308.1
	NHP2	NM_001396110.1		c.231-881G>T		intron	N/A	NP_001383039.1
	NHP2	NM_001034833.2		c.230+1617G>T		intron	N/A	NP_001030005.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHP2	ENST00000274606.8	TSL:1 MANE Select	c.231-881G>T		intron	N/A	ENSP00000274606.4
	NHP2	ENST00000514354.5	TSL:3	c.231-881G>T		intron	N/A	ENSP00000423803.1
	NHP2	ENST00000511078.1	TSL:2	c.231-881G>T		intron	N/A	ENSP00000423849.1

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

African (AFR) AF: 0.378 AC: 15643 AN: 41370

American (AMR) AF: 0.194 AC: 2957 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1001 AN: 3472

East Asian (EAS) AF: 0.300 AC: 1545 AN: 5152

South Asian (SAS) AF: 0.219 AC: 1053 AN: 4818

European-Finnish (FIN) AF: 0.120 AC: 1269 AN: 10564

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.199 AC: 13494 AN: 67942

Other (OTH) AF: 0.257 AC: 541 AN: 2108

Alfa AF: 0.186 Hom.: 1391

Bravo AF: 0.261

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.92
DANN	Benign	0.64
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13189047; hg19: chr5-177578875; COSMIC: COSV51071005; COSMIC: COSV51071005;