Genetic Variant PSMB5:c.349+7590A>G (chr14-23025778-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000555895.5(PSMB5):c.349+7590A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 918,650 control chromosomes in the GnomAD database, including 110,805 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 25780 hom., cov: 32)

Exomes 𝑓: 0.46 ( 85025 hom. )

Consequence

PSMB5
ENST00000555895.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.19

Publications

6 publications found

Variant links:

Genes affected

PSMB5 (HGNC:9542): (proteasome 20S subunit beta 5) 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 in the proteasome. This catalytic subunit is not present in the immunoproteasome and is replaced by catalytic subunit 3i (proteasome beta 8 subunit). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2009]

PSMB5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
PSMB5	NM_002797.5 link	c.*311A>G	downstream_gene_variant	ENST00000361611.11	NP_002788.1	P28074-1
PSMB5	NM_001144932.3 link	c.*576A>G	downstream_gene_variant		NP_001138404.1	P28074-2
PSMB5	NM_001130725.1 link	c.*311A>G	downstream_gene_variant		NP_001124197.1	P28074-3A0A140VJS7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMB5	ENST00000361611.11 link	c.*311A>G		downstream_gene_variant		1	NM_002797.5	ENSP00000355325.6		P28074-1

Frequencies

GnomAD3 genomes

AF:

0.549

AC:

83500

AN:

151996

Hom.:

25719

Cov.:

show subpopulations

Gnomad AFR

AF:

0.844

Gnomad AMI

AF:

0.386

Gnomad AMR

AF:

0.375

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.507

Gnomad FIN

AF:

0.443

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.462

Gnomad OTH

AF:

0.523

GnomAD4 exome

AF:

0.462

AC:

354036

AN:

766538

Hom.:

85025

AF XY:

0.463

AC XY:

172762

AN XY:

373510

show subpopulations

African (AFR)

AF:

0.868

AC:

14475

AN:

16684

American (AMR)

AF:

0.318

AC:

3120

AN:

9800

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

5105

AN:

10186

East Asian (EAS)

AF:

0.184

AC:

2927

AN:

15884

South Asian (SAS)

AF:

0.502

AC:

20822

AN:

41446

European-Finnish (FIN)

AF:

0.440

AC:

5344

AN:

12150

Middle Eastern (MID)

AF:

0.534

AC:

1085

AN:

2030

European-Non Finnish (NFE)

AF:

0.457

AC:

286986

AN:

627904

Other (OTH)

AF:

0.465

AC:

14172

AN:

30454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

8620

17240

25861

34481

43101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9502

19004

28506

38008

47510

<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:

0.550

AC:

83604

AN:

152112

Hom.:

25780

Cov.:

AF XY:

0.542

AC XY:

40277

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.845

AC:

35068

AN:

41524

American (AMR)

AF:

0.374

AC:

5713

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

1710

AN:

3470

East Asian (EAS)

AF:

0.194

AC:

1003

AN:

5178

South Asian (SAS)

AF:

0.505

AC:

2435

AN:

4820

European-Finnish (FIN)

AF:

0.443

AC:

4685

AN:

10576

Middle Eastern (MID)

AF:

0.521

AC:

152

AN:

292

European-Non Finnish (NFE)

AF:

0.462

AC:

31373

AN:

67966

Other (OTH)

AF:

0.528

AC:

1113

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1689

3378

5068

6757

8446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

684

1368

2052

2736

3420

<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:

0.532

Hom.:

3874

Bravo

AF:

0.554

Asia WGS

AF:

0.394

AC:

1375

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

2.2

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

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

Computational scores

Splicing

Publications

Other links and lift over