rs7172

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002796.3(PSMB4):c.75G>A(p.Pro25Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 1,613,768 control chromosomes in the GnomAD database, including 485,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 34866 hom., cov: 31)

Exomes 𝑓: 0.77 ( 450308 hom. )

Consequence

PSMB4
NM_002796.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0750

Publications

38 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:

ENSG00000307595 (HGNC:):

ENSG00000307595 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 1-151399662-G-A is Benign according to our data. Variant chr1-151399662-G-A is described in ClinVar as Benign. ClinVar VariationId is 1165733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.075 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMB4	NM_002796.3 link	c.75G>A	p.Pro25Pro	synonymous_variant	Exon 1 of 7	ENST00000290541.7	NP_002787.2	P28070A0A140VK46

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMB4	ENST00000290541.7 link	c.75G>A	p.Pro25Pro	synonymous_variant	Exon 1 of 7	1	NM_002796.3	ENSP00000290541.6		P28070

Frequencies

GnomAD3 genomes

AF:

0.643

AC:

97600

AN:

151854

Hom.:

34862

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.919

Gnomad AMR

AF:

0.558

Gnomad ASJ

AF:

0.802

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.679

Gnomad FIN

AF:

0.766

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.822

Gnomad OTH

AF:

0.682

GnomAD2 exomes

AF:

0.665

AC:

167147

AN:

251210

AF XY:

0.688

show subpopulations

Gnomad AFR exome

AF:

0.359

Gnomad AMR exome

AF:

0.397

Gnomad ASJ exome

AF:

0.791

Gnomad EAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.773

Gnomad NFE exome

AF:

0.822

Gnomad OTH exome

AF:

0.725

GnomAD4 exome

AF:

0.771

AC:

1127646

AN:

1461796

Hom.:

450308

Cov.:

AF XY:

0.772

AC XY:

561664

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.363

AC:

12165

AN:

33474

American (AMR)

AF:

0.415

AC:

18547

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.795

AC:

20790

AN:

26136

East Asian (EAS)

AF:

0.210

AC:

8348

AN:

39694

South Asian (SAS)

AF:

0.692

AC:

59680

AN:

86242

European-Finnish (FIN)

AF:

0.776

AC:

41444

AN:

53420

Middle Eastern (MID)

AF:

0.781

AC:

4496

AN:

5758

European-Non Finnish (NFE)

AF:

0.825

AC:

917208

AN:

1111978

Other (OTH)

AF:

0.745

AC:

44968

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

13571

27142

40712

54283

67854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20606

41212

61818

82424

103030

<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:

0.642

AC:

97624

AN:

151972

Hom.:

34866

Cov.:

AF XY:

0.638

AC XY:

47360

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.374

AC:

15499

AN:

41434

American (AMR)

AF:

0.558

AC:

8514

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.802

AC:

2785

AN:

3472

East Asian (EAS)

AF:

0.212

AC:

1087

AN:

5132

South Asian (SAS)

AF:

0.679

AC:

3272

AN:

4818

European-Finnish (FIN)

AF:

0.766

AC:

8088

AN:

10560

Middle Eastern (MID)

AF:

0.782

AC:

230

AN:

294

European-Non Finnish (NFE)

AF:

0.822

AC:

55867

AN:

67968

Other (OTH)

AF:

0.684

AC:

1444

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1436

2872

4307

5743

7179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

760

1520

2280

3040

3800

<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:

0.741

Hom.:

135213

Bravo

AF:

0.608

Asia WGS

AF:

0.507

AC:

1764

AN:

3478

EpiCase

AF:

0.817

EpiControl

AF:

0.819

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 29, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 79% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. -

PSMB4-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.0

(source)

DANN

Benign

0.89

PhyloP100

-0.075

PromoterAI

-0.018

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over