6-170553212-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP2BP4_StrongBA1

The NM_002793.4(PSMB1):c.31C>G(p.Pro11Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,611,798 control chromosomes in the GnomAD database, including 138,280 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 11809 hom., cov: 34)

Exomes 𝑓: 0.41 ( 126471 hom. )

Consequence

PSMB1
NM_002793.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0860

Publications

50 publications found

Variant links:

Genes affected

PSMB1 (HGNC:9537): (proteasome 20S subunit beta 1) 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 tightly linked to the TBP (TATA-binding protein) gene in human and in mouse, and is transcribed in the opposite orientation in both species. [provided by RefSeq, Jul 2008]

PSMB1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with microcephaly, hypotonia, and absent language
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

PSMB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.87488 (below the threshold of 3.09). Trascript score misZ: 0.6854 (below the threshold of 3.09). GenCC associations: The gene is linked to neurodevelopmental disorder with microcephaly, hypotonia, and absent language.

BP4

Computational evidence support a benign effect (MetaRNN=1.8062194E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMB1	NM_002793.4 link	c.31C>G	p.Pro11Ala	missense_variant	Exon 1 of 6	ENST00000262193.7	NP_002784.1	P20618A0A140VK45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMB1	ENST00000262193.7 link	c.31C>G	p.Pro11Ala	missense_variant	Exon 1 of 6	1	NM_002793.4	ENSP00000262193.6		P20618

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

58105

AN:

152032

Hom.:

11787

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.600

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.774

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.438

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.402

Gnomad OTH

AF:

0.389

GnomAD2 exomes

AF:

0.416

AC:

103433

AN:

248614

AF XY:

0.417

show subpopulations

Gnomad AFR exome

AF:

0.283

Gnomad AMR exome

AF:

0.365

Gnomad ASJ exome

AF:

0.336

Gnomad EAS exome

AF:

0.778

Gnomad FIN exome

AF:

0.433

Gnomad NFE exome

AF:

0.401

Gnomad OTH exome

AF:

0.389

GnomAD4 exome

AF:

0.410

AC:

598504

AN:

1459648

Hom.:

126471

Cov.:

AF XY:

0.410

AC XY:

297685

AN XY:

726096

show subpopulations

African (AFR)

AF:

0.279

AC:

9343

AN:

33446

American (AMR)

AF:

0.367

AC:

16357

AN:

44524

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

8624

AN:

26112

East Asian (EAS)

AF:

0.783

AC:

31063

AN:

39666

South Asian (SAS)

AF:

0.406

AC:

34941

AN:

86032

European-Finnish (FIN)

AF:

0.430

AC:

22919

AN:

53274

Middle Eastern (MID)

AF:

0.325

AC:

1855

AN:

5700

European-Non Finnish (NFE)

AF:

0.404

AC:

448875

AN:

1110580

Other (OTH)

AF:

0.407

AC:

24527

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

17271

34541

51812

69082

86353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14014

28028

42042

56056

70070

<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:

0.382

AC:

58170

AN:

152150

Hom.:

11809

Cov.:

AF XY:

0.387

AC XY:

28755

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.292

AC:

12115

AN:

41534

American (AMR)

AF:

0.363

AC:

5556

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

1104

AN:

3470

East Asian (EAS)

AF:

0.773

AC:

3986

AN:

5154

South Asian (SAS)

AF:

0.416

AC:

2005

AN:

4824

European-Finnish (FIN)

AF:

0.438

AC:

4640

AN:

10590

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.402

AC:

27292

AN:

67970

Other (OTH)

AF:

0.392

AC:

828

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1868

3735

5603

7470

9338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

566

1132

1698

2264

2830

<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:

0.401

Hom.:

9570

Bravo

AF:

0.380

TwinsUK

AF:

0.401

AC:

1487

ALSPAC

AF:

0.409

AC:

1577

ESP6500AA

AF:

0.297

AC:

1308

ESP6500EA

AF:

0.390

AC:

3350

ExAC

AF:

0.415

AC:

50443

Asia WGS

AF:

0.567

AC:

1969

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.4

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.041

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0000018

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

PhyloP100

0.086

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.13

REVEL

Benign

0.033

Sift

Benign

0.46

Sift4G

Benign

0.19

Polyphen

0.0

Vest4

0.041

MPC

0.30

ClinPred

0.0031

GERP RS

0.41

PromoterAI

0.00080

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.055

gMVP

0.43

Mutation Taster

=96/4

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over