Variant chr5-178153642-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017838.4(NHP2):c.160+16G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,782 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 42 hom., cov: 33)

Exomes 𝑓: 0.014 ( 264 hom. )

Consequence

NHP2
NM_017838.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.30

Variant links:

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 links:

NHP2 (HGNC:):

NHP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-178153642-C-G is Benign according to our data. Variant chr5-178153642-C-G is described in ClinVar as [Benign]. Clinvar id is 260941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-178153642-C-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
NHP2	NM_017838.4 linkuse as main transcript	c.160+16G>C	intron_variant	ENST00000274606.8	NP_060308.1	Q9NX24
NHP2	NM_001396110.1 linkuse as main transcript	c.160+16G>C	intron_variant		NP_001383039.1
NHP2	NM_001034833.2 linkuse as main transcript	c.160+16G>C	intron_variant		NP_001030005.1	Q9NX24J3QSY4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHP2	ENST00000274606.8 linkuse as main transcript	c.160+16G>C		intron_variant		1	NM_017838.4	ENSP00000274606.4		Q9NX24

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2594

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.00606

Gnomad EAS

AF:

0.0859

Gnomad SAS

AF:

0.00910

Gnomad FIN

AF:

0.00705

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.0172

AC:

4306

AN:

249626

Hom.:

100

AF XY:

0.0163

AC XY:

2206

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.0222

Gnomad AMR exome

AF:

0.00981

Gnomad ASJ exome

AF:

0.00768

Gnomad EAS exome

AF:

0.0922

Gnomad SAS exome

AF:

0.00651

Gnomad FIN exome

AF:

0.00657

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.0166

GnomAD4 exome

AF:

0.0137

AC:

20036

AN:

1461432

Hom.:

264

Cov.:

AF XY:

0.0134

AC XY:

9742

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.0223

Gnomad4 AMR exome

AF:

0.0112

Gnomad4 ASJ exome

AF:

0.00767

Gnomad4 EAS exome

AF:

0.0770

Gnomad4 SAS exome

AF:

0.00676

Gnomad4 FIN exome

AF:

0.00699

Gnomad4 NFE exome

AF:

0.0121

Gnomad4 OTH exome

AF:

0.0168

GnomAD4 genome

AF:

0.0170

AC:

2595

AN:

152350

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

1248

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0213

Gnomad4 AMR

AF:

0.0166

Gnomad4 ASJ

AF:

0.00606

Gnomad4 EAS

AF:

0.0859

Gnomad4 SAS

AF:

0.00890

Gnomad4 FIN

AF:

0.00705

Gnomad4 NFE

AF:

0.0121

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.00587

Hom.:

Bravo

AF:

0.0198

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 07, 2019

- -

Dyskeratosis congenita

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.8

DANN

Benign

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.5

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over