Variant 6-170548957-C-T 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.221+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,339,064 control chromosomes in the GnomAD database, including 185,909 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 0.58 ( 26370 hom., cov: 32)

Exomes 𝑓: 0.51 ( 159539 hom. )

Consequence

PSMB1
NM_002793.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.614

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=-0.98).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMB1	NM_002793.4 linkuse as main transcript	c.221+49G>A		intron_variant		ENST00000262193.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB1	ENST00000262193.7 linkuse as main transcript	c.221+49G>A		intron_variant		1	NM_002793.4	P1
PSMB1	ENST00000462957.1 linkuse as main transcript	n.1436+49G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87737

AN:

151882

Hom.:

26324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.748

Gnomad AMI

AF:

0.674

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.786

Gnomad SAS

AF:

0.483

Gnomad FIN

AF:

0.486

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.560

GnomAD3 exomes

AF:

0.530

AC:

120214

AN:

226740

Hom.:

32862

AF XY:

0.526

AC XY:

64459

AN XY:

122576

show subpopulations

Gnomad AFR exome

AF:

0.751

Gnomad AMR exome

AF:

0.453

Gnomad ASJ exome

AF:

0.541

Gnomad EAS exome

AF:

0.786

Gnomad SAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.481

Gnomad NFE exome

AF:

0.508

Gnomad OTH exome

AF:

0.517

GnomAD4 exome

AF:

0.514

AC:

610049

AN:

1187064

Hom.:

159539

Cov.:

AF XY:

0.513

AC XY:

308215

AN XY:

601316

show subpopulations

Gnomad4 AFR exome

AF:

0.759

Gnomad4 AMR exome

AF:

0.460

Gnomad4 ASJ exome

AF:

0.532

Gnomad4 EAS exome

AF:

0.791

Gnomad4 SAS exome

AF:

0.472

Gnomad4 FIN exome

AF:

0.481

Gnomad4 NFE exome

AF:

0.501

Gnomad4 OTH exome

AF:

0.531

GnomAD4 genome

AF:

0.578

AC:

87831

AN:

152000

Hom.:

26370

Cov.:

AF XY:

0.575

AC XY:

42677

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.749

Gnomad4 AMR

AF:

0.481

Gnomad4 ASJ

AF:

0.510

Gnomad4 EAS

AF:

0.785

Gnomad4 SAS

AF:

0.481

Gnomad4 FIN

AF:

0.486

Gnomad4 NFE

AF:

0.504

Gnomad4 OTH

AF:

0.561

Alfa

AF:

0.539

Hom.:

5626

Bravo

AF:

0.591

Asia WGS

AF:

0.635

AC:

2205

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.40

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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