Genetic Variant ENST00000495288.5:n.12C>T (chr1-151399571-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000495288.5(PSMB4):n.12C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 1,592,352 control chromosomes in the GnomAD database, including 8,497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.079 ( 1308 hom., cov: 31)

Exomes 𝑓: 0.035 ( 7189 hom. )

Consequence

PSMB4
ENST00000495288.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.680

Publications

13 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 1-151399571-C-T is Benign according to our data. Variant chr1-151399571-C-T is described in ClinVar as Benign. ClinVar VariationId is 2637879.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMB4	NM_002796.3 link	c.-17C>T		upstream_gene_variant		ENST00000290541.7	NP_002787.2	P28070A0A140VK46

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMB4	ENST00000290541.7 link	c.-17C>T		upstream_gene_variant		1	NM_002796.3	ENSP00000290541.6		P28070

Frequencies

GnomAD3 genomes

AF:

0.0792

AC:

12052

AN:

152108

Hom.:

1303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0758

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00369

Gnomad OTH

AF:

0.0703

GnomAD2 exomes

AF:

0.0977

AC:

22553

AN:

230762

AF XY:

0.0873

show subpopulations

Gnomad AFR exome

AF:

0.121

Gnomad AMR exome

AF:

0.315

Gnomad ASJ exome

AF:

0.0104

Gnomad EAS exome

AF:

0.404

Gnomad FIN exome

AF:

0.0703

Gnomad NFE exome

AF:

0.00465

Gnomad OTH exome

AF:

0.0725

GnomAD4 exome

AF:

0.0349

AC:

50253

AN:

1440126

Hom.:

7189

Cov.:

AF XY:

0.0352

AC XY:

25248

AN XY:

716294

show subpopulations

African (AFR)

AF:

0.125

AC:

3977

AN:

31832

American (AMR)

AF:

0.299

AC:

11129

AN:

37160

Ashkenazi Jewish (ASJ)

AF:

0.00939

AC:

235

AN:

25022

East Asian (EAS)

AF:

0.453

AC:

17906

AN:

39510

South Asian (SAS)

AF:

0.0884

AC:

7398

AN:

83718

European-Finnish (FIN)

AF:

0.0647

AC:

3439

AN:

53192

Middle Eastern (MID)

AF:

0.0207

AC:

117

AN:

5646

European-Non Finnish (NFE)

AF:

0.00245

AC:

2707

AN:

1104724

Other (OTH)

AF:

0.0564

AC:

3345

AN:

59322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1988

3976

5963

7951

9939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.0794

AC:

12090

AN:

152226

Hom.:

1308

Cov.:

AF XY:

0.0864

AC XY:

6433

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.117

AC:

4848

AN:

41542

American (AMR)

AF:

0.211

AC:

3227

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00662

AC:

AN:

3472

East Asian (EAS)

AF:

0.438

AC:

2251

AN:

5142

South Asian (SAS)

AF:

0.109

AC:

524

AN:

4822

European-Finnish (FIN)

AF:

0.0758

AC:

804

AN:

10610

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00371

AC:

252

AN:

68014

Other (OTH)

AF:

0.0734

AC:

155

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

481

962

1444

1925

2406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<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:

0.0367

Hom.:

2503

Bravo

AF:

0.0933

Asia WGS

AF:

0.271

AC:

941

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 14, 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 35% of patients studied by a panel of primary immunodeficiencies. Number of patients: 34. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

-0.68

PromoterAI

-0.12

Neutral

(source)

Mutation Taster

=300/0

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