rs2071476

chr6-32857602-A-G

Variant summary

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

The NM_002800.5(PSMB9):c.260+208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 566,432 control chromosomes in the GnomAD database, including 55,141 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 0.45 (15213 hom., cov: 33)
  • Exomes 𝑓: 0.44 (39928 hom.)
• Consequence: PSMB9 NM_002800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

Genes affected

PSMB9 (HGNC:9546): (proteasome 20S subunit beta 9) 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. This gene is located in the class II region of the MHC (major histocompatibility complex). Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 1 (proteasome beta 6 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMB9	NM_002800.5	c.260+208A>G		intron_variant		ENST00000374859.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB9	ENST00000374859.3	c.260+208A>G		intron_variant		1	NM_002800.5	P1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67762 AN: 151998 Hom.: 15193 Cov.: 33

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.451

GnomAD4 exome AF: 0.436 AC: 180565 AN: 414316 Hom.: 39928 Cov.: 5 AF XY: 0.435 AC XY: 93324 AN XY: 214312

Gnomad4 AFR exome AF: 0.484

Gnomad4 AMR exome AF: 0.440

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.367

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.427

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.451

GnomAD4 genome AF: 0.446 AC: 67828 AN: 152116 Hom.: 15213 Cov.: 33 AF XY: 0.443 AC XY: 32928 AN XY: 74370

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.450

Alfa AF: 0.443 Hom.: 22808

Bravo AF: 0.447

Asia WGS AF: 0.455 AC: 1583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.1
Dann	Benign	0.51

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: rs2071476; hg19: chr6-32825379; COSMIC: COSV62756143; COSMIC: COSV62756143;