Variant rs9357155 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_148919.4(PSMB8):c.537+63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,611,412 control chromosomes in the GnomAD database, including 12,384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1037 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11347 hom. )

Consequence

PSMB8
NM_148919.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0980

Variant links:

Genes affected

PSMB8 (HGNC:9545): (proteasome 20S subunit beta 8) 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 3 (proteasome beta 5 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit. Two alternative transcripts encoding two isoforms have been identified; both isoforms are processed to yield the same mature subunit. [provided by RefSeq, Jul 2008]

PSMB8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 6-32842071-G-A is Benign according to our data. Variant chr6-32842071-G-A is described in ClinVar as [Benign]. Clinvar id is 1277080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMB8	NM_148919.4 linkuse as main transcript	c.537+63C>T		intron_variant		ENST00000374882.8	NP_683720.2
PSMB8	NM_004159.5 linkuse as main transcript	c.525+63C>T		intron_variant			NP_004150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMB8	ENST00000374882.8 linkuse as main transcript	c.537+63C>T		intron_variant		1	NM_148919.4	ENSP00000364016	P1	P28062-1

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17011

AN:

152084

Hom.:

1037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0760

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.0836

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.0965

GnomAD4 exome

AF:

0.122

AC:

177891

AN:

1459210

Hom.:

11347

Cov.:

AF XY:

0.122

AC XY:

88695

AN XY:

726046

show subpopulations

Gnomad4 AFR exome

AF:

0.0746

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.0879

Gnomad4 EAS exome

AF:

0.140

Gnomad4 SAS exome

AF:

0.143

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.120

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.112

AC:

17007

AN:

152202

Hom.:

1037

Cov.:

AF XY:

0.113

AC XY:

8425

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0759

Gnomad4 AMR

AF:

0.140

Gnomad4 ASJ

AF:

0.0836

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.122

Gnomad4 NFE

AF:

0.119

Gnomad4 OTH

AF:

0.0945

Alfa

AF:

0.116

Hom.:

2054

Bravo

AF:

0.111

Asia WGS

AF:

0.112

AC:

389

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 14, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.6

DANN

Benign

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over