Variant rs10946279 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002793.4(PSMB1):c.-6C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 1,600,360 control chromosomes in the GnomAD database, including 2,357 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 0.056 ( 280 hom., cov: 33)

Exomes 𝑓: 0.050 ( 2077 hom. )

Consequence

PSMB1
NM_002793.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.79

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMB1	NM_002793.4 link	c.-6C>T		5_prime_UTR_premature_start_codon_gain_variant	1/6	ENST00000262193.7	NP_002784.1	P20618A0A140VK45
PSMB1	NM_002793.4 link	c.-6C>T		5_prime_UTR_variant	1/6	ENST00000262193.7	NP_002784.1	P20618A0A140VK45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMB1	ENST00000262193.7 link	c.-6C>T		5_prime_UTR_premature_start_codon_gain_variant	1/6	1	NM_002793.4	ENSP00000262193.6		P20618
PSMB1	ENST00000262193.7 link	c.-6C>T		5_prime_UTR_variant	1/6	1	NM_002793.4	ENSP00000262193.6		P20618

Frequencies

GnomAD3 genomes

AF:

0.0559

AC:

8509

AN:

152142

Hom.:

280

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0756

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0540

Gnomad ASJ

AF:

0.0703

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.00579

Gnomad FIN

AF:

0.0332

Gnomad MID

AF:

0.0732

Gnomad NFE

AF:

0.0554

Gnomad OTH

AF:

0.0550

GnomAD3 exomes

AF:

0.0428

AC:

10154

AN:

237012

Hom.:

283

AF XY:

0.0413

AC XY:

5288

AN XY:

128150

show subpopulations

Gnomad AFR exome

AF:

0.0775

Gnomad AMR exome

AF:

0.0357

Gnomad ASJ exome

AF:

0.0775

Gnomad EAS exome

AF:

0.00331

Gnomad SAS exome

AF:

0.00551

Gnomad FIN exome

AF:

0.0307

Gnomad NFE exome

AF:

0.0555

Gnomad OTH exome

AF:

0.0539

GnomAD4 exome

AF:

0.0496

AC:

71863

AN:

1448100

Hom.:

2077

Cov.:

AF XY:

0.0485

AC XY:

34904

AN XY:

720358

show subpopulations

Gnomad4 AFR exome

AF:

0.0792

Gnomad4 AMR exome

AF:

0.0371

Gnomad4 ASJ exome

AF:

0.0792

Gnomad4 EAS exome

AF:

0.00399

Gnomad4 SAS exome

AF:

0.00625

Gnomad4 FIN exome

AF:

0.0331

Gnomad4 NFE exome

AF:

0.0542

Gnomad4 OTH exome

AF:

0.0510

GnomAD4 genome

AF:

0.0559

AC:

8513

AN:

152260

Hom.:

280

Cov.:

AF XY:

0.0535

AC XY:

3982

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0755

Gnomad4 AMR

AF:

0.0539

Gnomad4 ASJ

AF:

0.0703

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.00580

Gnomad4 FIN

AF:

0.0332

Gnomad4 NFE

AF:

0.0554

Gnomad4 OTH

AF:

0.0544

Alfa

AF:

0.0534

Hom.:

425

Bravo

AF:

0.0577

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.072

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over