rs2296840

Positions:

• chr1-151399571-C-T

Variant summary

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

The ENST00000495288.5(PSMB4):​n.12C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 1,592,352 control chromosomes in the GnomAD database, including 8,497 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 0.079 (1308 hom., cov: 31)
  • Exomes 𝑓: 0.035 (7189 hom.)
• Consequence: PSMB4 ENST00000495288.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.680

Genes affected

PSMB4 (HGNC:9541): (proteasome 20S subunit beta 4) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMB4	NM_002796.3			upstream_gene_variant		ENST00000290541.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB4	ENST00000290541.7			upstream_gene_variant		1	NM_002796.3	P1

Frequencies

GnomAD3 genomes AF: 0.0792 AC: 12052 AN: 152108 Hom.: 1303 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0758

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00369

Gnomad OTH AF: 0.0703

GnomAD3 exomes AF: 0.0977 AC: 22553 AN: 230762 Hom.: 3263 AF XY: 0.0873 AC XY: 11008 AN XY: 126046

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.315

Gnomad ASJ exome AF: 0.0104

Gnomad EAS exome AF: 0.404

Gnomad SAS exome AF: 0.0929

Gnomad FIN exome AF: 0.0703

Gnomad NFE exome AF: 0.00465

Gnomad OTH exome AF: 0.0725

GnomAD4 exome AF: 0.0349 AC: 50253 AN: 1440126 Hom.: 7189 Cov.: 29 AF XY: 0.0352 AC XY: 25248 AN XY: 716294

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.299

Gnomad4 ASJ exome AF: 0.00939

Gnomad4 EAS exome AF: 0.453

Gnomad4 SAS exome AF: 0.0884

Gnomad4 FIN exome AF: 0.0647

Gnomad4 NFE exome AF: 0.00245

Gnomad4 OTH exome AF: 0.0564

GnomAD4 genome AF: 0.0794 AC: 12090 AN: 152226 Hom.: 1308 Cov.: 31 AF XY: 0.0864 AC XY: 6433 AN XY: 74436

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.00662

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0758

Gnomad4 NFE AF: 0.00371

Gnomad4 OTH AF: 0.0734

Alfa AF: 0.0289 Hom.: 842

Bravo AF: 0.0933

Asia WGS AF: 0.271 AC: 941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.94

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: rs2296840; hg19: chr1-151372047; COSMIC: COSV51852063; COSMIC: COSV51852063;