chr1-151399662-G-A

Position:

chr1-151399662-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002796.3(PSMB4):c.75G>A(p.Pro25=) 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
PSMB4	NM_002796.3 linkuse as main transcript	c.75G>A	p.Pro25=	synonymous_variant	1/7	ENST00000290541.7	NP_002787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMB4	ENST00000290541.7 linkuse as main transcript	c.75G>A	p.Pro25=	synonymous_variant	1/7	1	NM_002796.3	ENSP00000290541	P1

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

GnomAD3 exomes

AF:

0.665

AC:

167147

AN:

251210

Hom.:

61538

AF XY:

0.688

AC XY:

93534

AN XY:

135868

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 SAS exome

AF:

0.688

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

Gnomad4 AFR exome

AF:

0.363

Gnomad4 AMR exome

AF:

0.415

Gnomad4 ASJ exome

AF:

0.795

Gnomad4 EAS exome

AF:

0.210

Gnomad4 SAS exome

AF:

0.692

Gnomad4 FIN exome

AF:

0.776

Gnomad4 NFE exome

AF:

0.825

Gnomad4 OTH exome

AF:

0.745

GnomAD4 genome

AF:

0.642

AC:

97624

AN:

151972

Hom.:

34866

Cov.:

AF XY:

0.638

AC XY:

47360

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.374

Gnomad4 AMR

AF:

0.558

Gnomad4 ASJ

AF:

0.802

Gnomad4 EAS

AF:

0.212

Gnomad4 SAS

AF:

0.679

Gnomad4 FIN

AF:

0.766

Gnomad4 NFE

AF:

0.822

Gnomad4 OTH

AF:

0.684

Alfa

AF:

0.775

Hom.:

61278

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 29, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.0

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over