1-151401549-T-C

Position:

chr1-151401549-T-C

Variant summary

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

The NM_002796.3(PSMB4):c.701T>C(p.Ile234Thr) variant causes a missense change. The variant allele was found at a frequency of 0.176 in 1,608,884 control chromosomes in the GnomAD database, including 26,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar. Synonymous variant affecting the same amino acid position (i.e. I234I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.16 ( 2158 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24554 hom. )

Consequence

PSMB4
NM_002796.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.82

Variant links:

Genes affected

PSMB4 (HGNC:9541): (proteasome 20S subunit beta 4) 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. [provided by RefSeq, Jul 2008]

PSMB4 links:

PSMB4 (HGNC:):

PSMB4 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 (MetaRNN=0.0018168688).

BP6

Variant 1-151401549-T-C is Benign according to our data. Variant chr1-151401549-T-C is described in ClinVar as [Benign]. Clinvar id is 1166562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMB4	NM_002796.3 linkuse as main transcript	c.701T>C	p.Ile234Thr	missense_variant	6/7	ENST00000290541.7	NP_002787.2	P28070A0A140VK46

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMB4	ENST00000290541.7 linkuse as main transcript	c.701T>C	p.Ile234Thr	missense_variant	6/7	1	NM_002796.3	ENSP00000290541.6		P28070

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23849

AN:

152042

Hom.:

2155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0878

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.163

GnomAD3 exomes

AF:

0.198

AC:

49831

AN:

251478

Hom.:

5629

AF XY:

0.196

AC XY:

26657

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0866

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.199

Gnomad EAS exome

AF:

0.361

Gnomad SAS exome

AF:

0.219

Gnomad FIN exome

AF:

0.158

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.186

GnomAD4 exome

AF:

0.178

AC:

259495

AN:

1456724

Hom.:

24554

Cov.:

AF XY:

0.179

AC XY:

129972

AN XY:

724998

show subpopulations

Gnomad4 AFR exome

AF:

0.0772

Gnomad4 AMR exome

AF:

0.252

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.325

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.171

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.157

AC:

23852

AN:

152160

Hom.:

2158

Cov.:

AF XY:

0.158

AC XY:

11772

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0876

Gnomad4 AMR

AF:

0.189

Gnomad4 ASJ

AF:

0.191

Gnomad4 EAS

AF:

0.338

Gnomad4 SAS

AF:

0.209

Gnomad4 FIN

AF:

0.157

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.178

Hom.:

6471

Bravo

AF:

0.162

TwinsUK

AF:

0.156

AC:

578

ALSPAC

AF:

0.175

AC:

673

ESP6500AA

AF:

0.0942

AC:

415

ESP6500EA

AF:

0.173

AC:

1486

ExAC

AF:

0.194

AC:

23508

Asia WGS

AF:

0.182

AC:

632

AN:

3478

EpiCase

AF:

0.177

EpiControl

AF:

0.176

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -

PSMB4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Proteasome-associated autoinflammatory syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.84

MutationAssessor

Pathogenic

2.9

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.33

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.011

Polyphen

0.84

Vest4

0.28

MPC

0.66

ClinPred

0.047

GERP RS

6.0

Varity_R

0.63

gMVP

0.95

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