rs10946279

chr6-170553248-G-Achr6-170553248-G-C

Variant summary

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

The NM_002793.4(PSMB1):c.-6C>T variant causes a 5 prime UTR 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

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]

ACMG classification

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	UniProt
PSMB1	NM_002793.4	c.-6C>T		5_prime_UTR_variant	1/6	ENST00000262193.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB1	ENST00000262193.7	c.-6C>T		5_prime_UTR_variant	1/6	1	NM_002793.4	P1

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 8509 AN: 152142 Hom.: 280 Cov.: 33

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

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.: 28 AF XY: 0.0485 AC XY: 34904 AN XY: 720358

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.: 33 AF XY: 0.0535 AC XY: 3982 AN XY: 74442

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: 39 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

Other links and lift over

dbSNP: rs10946279; hg19: chr6-170862336;