rs7572505

Variant names:

• chr2-202287632-G-A
• rs7572505
• NM_015934.5:c.435-28G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-202287632-G-A
• chr2-202287632-G-C
• chr2-202287632-G-T

Variant summary

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

The NM_015934.5(NOP58):​c.435-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,564,552 control chromosomes in the GnomAD database, including 60,469 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.34 (10063 hom., cov: 32)
  • Exomes 𝑓: 0.26 (50406 hom.)
• Consequence: NOP58 NM_015934.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359
• Publications: 11 publications found

Genes affected

NOP58 (HGNC:29926): (NOP58 ribonucleoprotein) The protein encoded by this gene is a core component of box C/D small nucleolar ribonucleoproteins. Some box C/D small nucleolar RNAs (snoRNAs), such as U3, U8, and U14, are dependent upon the encoded protein for their synthesis. This protein is SUMOylated, which is necessary for high affinity binding to snoRNAs. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOP58	NM_015934.5	c.435-28G>A		intron_variant	Intron 5 of 14	ENST00000264279.10	NP_057018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOP58	ENST00000264279.10	c.435-28G>A		intron_variant	Intron 5 of 14	1	NM_015934.5	ENSP00000264279.5
NOP58	ENST00000433543.2	n.45-28G>A		intron_variant	Intron 1 of 6	3		ENSP00000388126.1
NOP58	ENST00000478941.1	n.459-2691G>A		intron_variant	Intron 3 of 3	3
NOP58	ENST00000492688.5	n.341-28G>A		intron_variant	Intron 4 of 6	4

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51049 AN: 151762 Hom.: 10045 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.305

GnomAD2 exomes AF: 0.280 AC: 70081 AN: 250234 AF XY: 0.276

Gnomad AFR exome AF: 0.556

Gnomad AMR exome AF: 0.324

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.130

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.239

GnomAD4 exome AF: 0.258 AC: 363933 AN: 1412672 Hom.: 50406 Cov.: 23 AF XY: 0.259 AC XY: 182531 AN XY: 705750

African (AFR) AF: 0.552 AC: 17995 AN: 32610

American (AMR) AF: 0.320 AC: 14217 AN: 44402

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 3588 AN: 25760

East Asian (EAS) AF: 0.0897 AC: 3532 AN: 39382

South Asian (SAS) AF: 0.356 AC: 30232 AN: 84990

European-Finnish (FIN) AF: 0.298 AC: 15850 AN: 53234

Middle Eastern (MID) AF: 0.225 AC: 1276 AN: 5666

European-Non Finnish (NFE) AF: 0.245 AC: 261582 AN: 1067906

Other (OTH) AF: 0.267 AC: 15661 AN: 58722

GnomAD4 genome AF: 0.337 AC: 51112 AN: 151880 Hom.: 10063 Cov.: 32 AF XY: 0.336 AC XY: 24963 AN XY: 74208

African (AFR) AF: 0.547 AC: 22673 AN: 41422

American (AMR) AF: 0.319 AC: 4860 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3464

East Asian (EAS) AF: 0.118 AC: 613 AN: 5176

South Asian (SAS) AF: 0.350 AC: 1684 AN: 4806

European-Finnish (FIN) AF: 0.301 AC: 3168 AN: 10514

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16796 AN: 67944

Other (OTH) AF: 0.302 AC: 637 AN: 2106

Alfa AF: 0.257 Hom.: 7336

Bravo AF: 0.345

Asia WGS AF: 0.287 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		0.36
BranchPoint Hunter		0.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7572505; hg19: chr2-203152355; COSMIC: COSV51896762; COSMIC: COSV51896762;