6-32857602-A-G

Variant names:

• chr6-32857602-A-G
• rs2071476
• NM_002800.5:c.260+208A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 32 publications found

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]

PSMB9 Gene-Disease associations (from GenCC):

• proteasome-associated autoinflammatory syndrome 3

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PSMB9	NM_002800.5	c.260+208A>G		intron_variant	Intron 3 of 5	ENST00000374859.3	NP_002791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMB9	ENST00000374859.3	c.260+208A>G		intron_variant	Intron 3 of 5	1	NM_002800.5	ENSP00000363993.2

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

African (AFR) AF: 0.484 AC: 5517 AN: 11388

American (AMR) AF: 0.440 AC: 6141 AN: 13952

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 5760 AN: 12476

East Asian (EAS) AF: 0.367 AC: 10444 AN: 28494

South Asian (SAS) AF: 0.431 AC: 13040 AN: 30256

European-Finnish (FIN) AF: 0.427 AC: 11500 AN: 26920

Middle Eastern (MID) AF: 0.525 AC: 972 AN: 1850

European-Non Finnish (NFE) AF: 0.439 AC: 116410 AN: 265066

Other (OTH) AF: 0.451 AC: 10781 AN: 23914

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

African (AFR) AF: 0.480 AC: 19889 AN: 41460

American (AMR) AF: 0.433 AC: 6621 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1554 AN: 3472

East Asian (EAS) AF: 0.376 AC: 1944 AN: 5176

South Asian (SAS) AF: 0.418 AC: 2015 AN: 4826

European-Finnish (FIN) AF: 0.416 AC: 4404 AN: 10584

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29893 AN: 67998

Other (OTH) AF: 0.450 AC: 952 AN: 2114

Alfa AF: 0.444 Hom.: 57011

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
PhyloP100		-0.20
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: rs2071476; hg19: chr6-32825379; COSMIC: COSV62756143;