6-170548957-C-T

Position:

• chr6-170548957-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614

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 (HGNC:):

ACMG classification

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	Protein	UniProt
PSMB1	NM_002793.4	c.221+49G>A		intron_variant		ENST00000262193.7	NP_002784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMB1	ENST00000262193.7	c.221+49G>A		intron_variant		1	NM_002793.4	ENSP00000262193.6
PSMB1	ENST00000462957.1	n.1436+49G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87737 AN: 151882 Hom.: 26324 Cov.: 32

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

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.: 15 AF XY: 0.513 AC XY: 308215 AN XY: 601316

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.: 32 AF XY: 0.575 AC XY: 42677 AN XY: 74282

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

Other links and lift over

dbSNP: rs2076319; hg19: chr6-170858045; COSMIC: COSV51532346;