rs991760

Variant names:

• chr6-32855790-G-A
• rs991760
• NM_002800.5:c.61-348G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-32855790-G-A
• chr6-32855790-G-C
• chr6-32855790-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002800.5(PSMB9):​c.61-348G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0837 in 152,054 control chromosomes in the GnomAD database, including 627 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 0.084 (627 hom., cov: 32)
• Consequence: PSMB9 NM_002800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 30 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMB9	NM_002800.5	c.61-348G>A		intron_variant	Intron 1 of 5	ENST00000374859.3	NP_002791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMB9	ENST00000374859.3	c.61-348G>A		intron_variant	Intron 1 of 5	1	NM_002800.5	ENSP00000363993.2
PSMB9	ENST00000395330.6	c.-9-348G>A		intron_variant	Intron 1 of 5	3		ENSP00000378739.1
PSMB9	ENST00000414474.5	c.-9-348G>A		intron_variant	Intron 1 of 4	5		ENSP00000394363.1
PSMB9	ENST00000464863.1	n.143-348G>A		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12686 AN: 151936 Hom.: 616 Cov.: 32

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0800

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0659

Gnomad OTH AF: 0.0780

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0837 AC: 12734 AN: 152054 Hom.: 627 Cov.: 32 AF XY: 0.0878 AC XY: 6524 AN XY: 74336

African (AFR) AF: 0.0909 AC: 3766 AN: 41446

American (AMR) AF: 0.103 AC: 1580 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 204 AN: 3472

East Asian (EAS) AF: 0.171 AC: 884 AN: 5178

South Asian (SAS) AF: 0.157 AC: 758 AN: 4822

European-Finnish (FIN) AF: 0.0800 AC: 844 AN: 10554

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0659 AC: 4480 AN: 67988

Other (OTH) AF: 0.0819 AC: 172 AN: 2100

Alfa AF: 0.0743 Hom.: 2007

Bravo AF: 0.0835

Asia WGS AF: 0.174 AC: 602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.10
DANN	Benign	0.65
PhyloP100		-1.7
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: rs991760; hg19: chr6-32823567;