rs201274409

Variant names:

• chr5-178153647-G-A
• rs201274409
• NM_017838.4:c.160+11C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-178153647-G-A
• chr5-178153647-G-C
• chr5-178153647-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_017838.4(NHP2):​c.160+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,613,176 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (4 hom.)
• Consequence: NHP2 NM_017838.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.91

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

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-178153647-G-A is Benign according to our data. Variant chr5-178153647-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 353026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-178153647-G-A is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHP2	NM_017838.4	c.160+11C>T		intron_variant	Intron 1 of 3	ENST00000274606.8	NP_060308.1
NHP2	NM_001396110.1	c.160+11C>T		intron_variant	Intron 1 of 4		NP_001383039.1
NHP2	NM_001034833.2	c.160+11C>T		intron_variant	Intron 1 of 2		NP_001030005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHP2	ENST00000274606.8	c.160+11C>T		intron_variant	Intron 1 of 3	1	NM_017838.4	ENSP00000274606.4

Frequencies

GnomAD3 genomes AF: 0.00136 AC: 207 AN: 152136 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00216

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00148 AC: 370 AN: 249610 AF XY: 0.00157

Gnomad AFR exome AF: 0.000382

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.0000998

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00190

Gnomad NFE exome AF: 0.00263

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00197 AC: 2876 AN: 1460922 Hom.: 4 Cov.: 31 AF XY: 0.00192 AC XY: 1394 AN XY: 726794

Gnomad4 AFR exome AF: 0.000568 AC: 19 AN: 33462

Gnomad4 AMR exome AF: 0.000246 AC: 11 AN: 44654

Gnomad4 ASJ exome AF: 0.0000766 AC: 2 AN: 26096

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39682

Gnomad4 SAS exome AF: 0.000290 AC: 25 AN: 86210

Gnomad4 FIN exome AF: 0.00210 AC: 112 AN: 53354

Gnomad4 NFE exome AF: 0.00235 AC: 2610 AN: 1111346

Gnomad4 Remaining exome AF: 0.00161 AC: 97 AN: 60354

GnomAD4 genome AF: 0.00135 AC: 206 AN: 152254 Hom.: 0 Cov.: 33 AF XY: 0.00117 AC XY: 87 AN XY: 74450

Gnomad4 AFR AF: 0.000433 AC: 0.00043315 AN: 0.00043315

Gnomad4 AMR AF: 0.000654 AC: 0.000653851 AN: 0.000653851

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000414 AC: 0.000413907 AN: 0.000413907

Gnomad4 FIN AF: 0.00264 AC: 0.00263803 AN: 0.00263803

Gnomad4 NFE AF: 0.00216 AC: 0.00216208 AN: 0.00216208

Gnomad4 OTH AF: 0.000474 AC: 0.000474383 AN: 0.000474383

Alfa AF: 0.00147 Hom.: 0

Bravo AF: 0.00116

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dyskeratosis congenita Benign:2

Oct 23, 2020

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Oct 12, 2015

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism

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: rs201274409; hg19: chr5-177580648;