rs6914744

chr6-170549432-A-Cchr6-170549432-A-Gchr6-170549432-A-T

Variant summary

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

The NM_002793.4(PSMB1):c.114-319T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 228,022 control chromosomes in the GnomAD database, including 23,709 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 0.44 (15083 hom., cov: 33)
  • Exomes 𝑓: 0.46 (8626 hom.)
• Consequence: PSMB1 NM_002793.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMB1	NM_002793.4	c.114-319T>G		intron_variant		ENST00000262193.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB1	ENST00000262193.7	c.114-319T>G		intron_variant		1	NM_002793.4	P1
PSMB1	ENST00000462957.1	n.1010T>G		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66590 AN: 151910 Hom.: 15059 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.444

GnomAD4 exome AF: 0.463 AC: 35172 AN: 75994 Hom.: 8626 Cov.: 0 AF XY: 0.464 AC XY: 18131 AN XY: 39102

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.428

Gnomad4 ASJ exome AF: 0.403

Gnomad4 EAS exome AF: 0.781

Gnomad4 SAS exome AF: 0.399

Gnomad4 FIN exome AF: 0.448

Gnomad4 NFE exome AF: 0.449

Gnomad4 OTH exome AF: 0.441

GnomAD4 genome AF: 0.438 AC: 66658 AN: 152028 Hom.: 15083 Cov.: 33 AF XY: 0.441 AC XY: 32754 AN XY: 74324

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.447

Alfa AF: 0.439 Hom.: 1854

Bravo AF: 0.438

Asia WGS AF: 0.576 AC: 2003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.6
Dann	Benign	0.34

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: rs6914744; hg19: chr6-170858520;