rs151227

chr16-28538187-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012385.3(NUPR1):c.113-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,596 control chromosomes in the GnomAD database, including 11,531 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 0.11 (970 hom., cov: 31)
  • Exomes 𝑓: 0.12 (10561 hom.)
• Consequence: NUPR1 NM_012385.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399

Genes affected

NUPR1 (HGNC:29990): (nuclear protein 1, transcriptional regulator) Enables DNA binding activity and transcription coactivator activity. Involved in several processes, including regulation of cellular catabolic process; regulation of generation of precursor metabolites and energy; and regulation of programmed cell death. Acts upstream of or within negative regulation of cell cycle. Located in intercellular bridge; nucleoplasm; and perinuclear region of cytoplasm. Part of protein-DNA complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUPR1	NM_012385.3	c.113-32C>T		intron_variant		ENST00000324873.8
NUPR1	NM_001042483.2	c.135C>T	p.Pro45=	synonymous_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUPR1	ENST00000324873.8	c.113-32C>T		intron_variant		1	NM_012385.3	P1
NUPR1	ENST00000395641.2	c.135C>T	p.Pro45=	synonymous_variant	2/3	2
NUPR1	ENST00000567646.1	c.*110-32C>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16339 AN: 151986 Hom.: 970 Cov.: 31

Gnomad AFR AF: 0.0860

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0979

Gnomad FIN AF: 0.0908

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.133

GnomAD3 exomes AF: 0.100 AC: 25064 AN: 250438 Hom.: 1462 AF XY: 0.103 AC XY: 13925 AN XY: 135378

Gnomad AFR exome AF: 0.0853

Gnomad AMR exome AF: 0.0672

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.000816

Gnomad SAS exome AF: 0.0988

Gnomad FIN exome AF: 0.0894

Gnomad NFE exome AF: 0.124

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.117 AC: 170451 AN: 1461492 Hom.: 10561 Cov.: 32 AF XY: 0.117 AC XY: 84745 AN XY: 727056

Gnomad4 AFR exome AF: 0.0891

Gnomad4 AMR exome AF: 0.0697

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.000554

Gnomad4 SAS exome AF: 0.0986

Gnomad4 FIN exome AF: 0.0873

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.107 AC: 16339 AN: 152104 Hom.: 970 Cov.: 31 AF XY: 0.105 AC XY: 7833 AN XY: 74350

Gnomad4 AFR AF: 0.0858

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0984

Gnomad4 FIN AF: 0.0908

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.132

Alfa AF: 0.122 Hom.: 1568

Bravo AF: 0.109

Asia WGS AF: 0.0500 AC: 173 AN: 3478

EpiCase AF: 0.137

EpiControl AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.1
Dann	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs151227; hg19: chr16-28549508; COSMIC: COSV61404853;