rs1474642

Positions:

• chr6-170543473-A-G

Variant summary

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

The NM_002793.4(PSMB1):​c.433+128T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,026,384 control chromosomes in the GnomAD database, including 10,785 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 0.13 (1545 hom., cov: 32)
  • Exomes 𝑓: 0.14 (9240 hom.)
• Consequence: PSMB1 NM_002793.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167

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 (AMR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMB1	NM_002793.4	c.433+128T>C		intron_variant		ENST00000262193.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB1	ENST00000262193.7	c.433+128T>C		intron_variant		1	NM_002793.4	P1
PSMB1	ENST00000462957.1	n.1648+128T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19283 AN: 152042 Hom.: 1542 Cov.: 32

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0389

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.139 AC: 121173 AN: 874222 Hom.: 9240 AF XY: 0.138 AC XY: 60154 AN XY: 435714

Gnomad4 AFR exome AF: 0.0496

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.0507

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.127 AC: 19291 AN: 152162 Hom.: 1545 Cov.: 32 AF XY: 0.133 AC XY: 9861 AN XY: 74384

Gnomad4 AFR AF: 0.0560

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.0386

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.142

Alfa AF: 0.136 Hom.: 1613

Bravo AF: 0.124

Asia WGS AF: 0.103 AC: 358 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.5
DANN	Benign	0.72

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: rs1474642; hg19: chr6-170852561; COSMIC: COSV51531831;