1-151401549-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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 the same amino acid substitution has been previously reported as Likely benign in 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

Publications

51 publications found

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 Gene-Disease associations (from GenCC):

proteasome-associated autoinflammatory syndrome 3
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

PSMB4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002796.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB4	NM_002796.3	MANE Select	c.701T>C	p.Ile234Thr	missense	Exon 6 of 7	NP_002787.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PSMB4	ENST00000290541.7	TSL:1 MANE Select	c.701T>C	p.Ile234Thr	missense	Exon 6 of 7	ENSP00000290541.6
PSMB4	ENST00000933662.1		c.584T>C	p.Ile195Thr	missense	Exon 5 of 6	ENSP00000603721.1
PSMB4	ENST00000933663.1		c.494T>C	p.Ile165Thr	missense	Exon 5 of 6	ENSP00000603722.1

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

GnomAD2 exomes

AF:

0.198

AC:

49831

AN:

251478

AF XY:

0.196

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 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

African (AFR)

AF:

0.0772

AC:

2579

AN:

33394

American (AMR)

AF:

0.252

AC:

11271

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

5094

AN:

26118

East Asian (EAS)

AF:

0.325

AC:

12887

AN:

39654

South Asian (SAS)

AF:

0.218

AC:

18737

AN:

86130

European-Finnish (FIN)

AF:

0.159

AC:

8516

AN:

53416

Middle Eastern (MID)

AF:

0.177

AC:

1021

AN:

5764

European-Non Finnish (NFE)

AF:

0.171

AC:

189303

AN:

1107292

Other (OTH)

AF:

0.167

AC:

10087

AN:

60242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

10843

21685

32528

43370

54213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6792

13584

20376

27168

33960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.157

AC:

23852

AN:

152160

Hom.:

2158

Cov.:

AF XY:

0.158

AC XY:

11772

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0876

AC:

3636

AN:

41508

American (AMR)

AF:

0.189

AC:

2886

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

664

AN:

3470

East Asian (EAS)

AF:

0.338

AC:

1747

AN:

5170

South Asian (SAS)

AF:

0.209

AC:

1007

AN:

4822

European-Finnish (FIN)

AF:

0.157

AC:

1669

AN:

10600

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.173

AC:

11777

AN:

67992

Other (OTH)

AF:

0.160

AC:

338

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1010

2020

3029

4039

5049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.175

Hom.:

11213

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Proteasome-associated autoinflammatory syndrome 3 (1)

PSMB4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

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

PhyloP100

4.8

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

Mutation Taster

=71/29

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over