rs941717

chr14-23025778-T-C

Variant summary

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

The ENST00000555895.5(PSMB5):c.351+7590A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 918,650 control chromosomes in the GnomAD database, including 110,805 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 0.55 (25780 hom., cov: 32)
  • Exomes 𝑓: 0.46 (85025 hom.)
• Consequence: PSMB5 ENST00000555895.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19

Genes affected

PSMB5 (HGNC:9542): (proteasome 20S subunit beta 5) 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 in the proteasome. This catalytic subunit is not present in the immunoproteasome and is replaced by catalytic subunit 3i (proteasome beta 8 subunit). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB5	ENST00000555895.5	c.351+7590A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83500 AN: 151996 Hom.: 25719 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.462 AC: 354036 AN: 766538 Hom.: 85025 AF XY: 0.463 AC XY: 172762 AN XY: 373510

Gnomad4 AFR exome AF: 0.868

Gnomad4 AMR exome AF: 0.318

Gnomad4 ASJ exome AF: 0.501

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.502

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.457

Gnomad4 OTH exome AF: 0.465

GnomAD4 genome AF: 0.550 AC: 83604 AN: 152112 Hom.: 25780 Cov.: 32 AF XY: 0.542 AC XY: 40277 AN XY: 74336

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.528

Alfa AF: 0.522 Hom.: 3602

Bravo AF: 0.554

Asia WGS AF: 0.394 AC: 1375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	18
Dann	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs941717; hg19: chr14-23494987;