Variant rs371173524 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_017838.4(NHP2):c.-10G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,602,630 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

NHP2
NM_017838.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.14

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 5-178153827-C-A is Benign according to our data. Variant chr5-178153827-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 353029.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
NHP2	NM_017838.4 linkuse as main transcript	c.-10G>T	5_prime_UTR_variant	1/4	ENST00000274606.8
NHP2	NM_001034833.2 linkuse as main transcript	c.-10G>T	5_prime_UTR_variant	1/3
NHP2	NM_001396110.1 linkuse as main transcript	c.-10G>T	5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHP2	ENST00000274606.8 linkuse as main transcript	c.-10G>T		5_prime_UTR_variant	1/4	1	NM_017838.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.000175

AC:

AN:

223090

Hom.:

AF XY:

0.000180

AC XY:

AN XY:

121970

show subpopulations

Gnomad AFR exome

AF:

0.000456

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000222

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000194

AC:

282

AN:

1450266

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

142

AN XY:

720840

show subpopulations

Gnomad4 AFR exome

AF:

0.000934

Gnomad4 AMR exome

AF:

0.000422

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000173

Gnomad4 OTH exome

AF:

0.000518

GnomAD4 genome

AF:

0.000341

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00378

Bravo

AF:

0.000438

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

Cadd

Benign

2.6

Dann

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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