rs2071480

Variant names:

• chr6-32854082-C-A
• rs2071480
• ENST00000395330.6:c.-9-2056C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-32854082-C-A
• chr6-32854082-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000395330.6(PSMB9):​c.-9-2056C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 999,508 control chromosomes in the GnomAD database, including 86,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (13411 hom., cov: 32)
  • Exomes 𝑓: 0.41 (72741 hom.)
• Consequence: PSMB9 ENST00000395330.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.645
• Publications: 28 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 6-32854082-C-A is Benign according to our data. Variant chr6-32854082-C-A is described in ClinVar as Benign. ClinVar VariationId is 1170127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMB9	NM_002800.5	c.-148C>A		upstream_gene_variant		ENST00000374859.3	NP_002791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMB9	ENST00000395330.6	c.-9-2056C>A		intron_variant	Intron 1 of 5	3		ENSP00000378739.1
PSMB9	ENST00000414474.5	c.-9-2056C>A		intron_variant	Intron 1 of 4	5		ENSP00000394363.1
PSMB9	ENST00000374859.3	c.-148C>A		upstream_gene_variant		1	NM_002800.5	ENSP00000363993.2
PSMB9	ENST00000464863.1	n.-66C>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63423 AN: 151866 Hom.: 13391 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.411 AC: 348305 AN: 847524 Hom.: 72741 Cov.: 11 AF XY: 0.411 AC XY: 175987 AN XY: 428640

African (AFR) AF: 0.439 AC: 8627 AN: 19634

American (AMR) AF: 0.422 AC: 8833 AN: 20934

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 7564 AN: 16504

East Asian (EAS) AF: 0.357 AC: 11753 AN: 32964

South Asian (SAS) AF: 0.383 AC: 21418 AN: 55870

European-Finnish (FIN) AF: 0.380 AC: 15720 AN: 41370

Middle Eastern (MID) AF: 0.512 AC: 1444 AN: 2822

European-Non Finnish (NFE) AF: 0.415 AC: 256427 AN: 618634

Other (OTH) AF: 0.426 AC: 16519 AN: 38792

GnomAD4 genome AF: 0.418 AC: 63488 AN: 151984 Hom.: 13411 Cov.: 32 AF XY: 0.414 AC XY: 30741 AN XY: 74298

African (AFR) AF: 0.442 AC: 18312 AN: 41470

American (AMR) AF: 0.414 AC: 6327 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1551 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1835 AN: 5156

South Asian (SAS) AF: 0.387 AC: 1861 AN: 4814

European-Finnish (FIN) AF: 0.368 AC: 3886 AN: 10560

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28316 AN: 67910

Other (OTH) AF: 0.426 AC: 897 AN: 2108

Alfa AF: 0.364 Hom.: 1826

Bravo AF: 0.421

Asia WGS AF: 0.421 AC: 1468 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MHC class I deficiency Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.62
PhyloP100		0.65
PromoterAI		-0.16	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2071480; hg19: chr6-32821859;