rs991760

chr6-32855790-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.94).
• 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/exons	MANE	UniProt
PSMB9	NM_002800.5	c.61-348G>A		intron_variant		ENST00000374859.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB9	ENST00000374859.3	c.61-348G>A		intron_variant		1	NM_002800.5	P1
PSMB9	ENST00000395330.5	c.-9-348G>A		intron_variant		3
PSMB9	ENST00000414474.5	c.-9-348G>A		intron_variant		5
PSMB9	ENST00000464863.1	n.143-348G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0909

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0588

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0800

Gnomad4 NFE AF: 0.0659

Gnomad4 OTH AF: 0.0819

Alfa AF: 0.0719 Hom.: 866

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

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: rs991760; hg19: chr6-32823567;