rs941718

Variant names:

• chr14-23025839-T-C
• rs941718
• ENST00000555895.5:c.349+7529A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000555895.5(PSMB5):​c.349+7529A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,345,932 control chromosomes in the GnomAD database, including 75,493 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 0.42 (17426 hom., cov: 31)
  • Exomes 𝑓: 0.30 (58067 hom.)
• Consequence: PSMB5 ENST00000555895.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.622
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMB5	NM_002797.5	c.*250A>G		downstream_gene_variant		ENST00000361611.11	NP_002788.1
PSMB5	NM_001144932.3	c.*515A>G		downstream_gene_variant			NP_001138404.1
PSMB5	NM_001130725.1	c.*250A>G		downstream_gene_variant			NP_001124197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMB5	ENST00000361611.11	c.*250A>G		downstream_gene_variant		1	NM_002797.5	ENSP00000355325.6

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63892 AN: 151930 Hom.: 17364 Cov.: 31

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.0713

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.297 AC: 354015 AN: 1193884 Hom.: 58067 Cov.: 26 AF XY: 0.299 AC XY: 172061 AN XY: 575240

African (AFR) AF: 0.805 AC: 21310 AN: 26464

American (AMR) AF: 0.220 AC: 3604 AN: 16364

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 6289 AN: 16574

East Asian (EAS) AF: 0.0503 AC: 1414 AN: 28088

South Asian (SAS) AF: 0.400 AC: 23346 AN: 58302

European-Finnish (FIN) AF: 0.306 AC: 6665 AN: 21780

Middle Eastern (MID) AF: 0.444 AC: 1433 AN: 3224

European-Non Finnish (NFE) AF: 0.281 AC: 274061 AN: 974780

Other (OTH) AF: 0.329 AC: 15893 AN: 48308

GnomAD4 genome AF: 0.421 AC: 64004 AN: 152048 Hom.: 17426 Cov.: 31 AF XY: 0.416 AC XY: 30918 AN XY: 74310

African (AFR) AF: 0.779 AC: 32310 AN: 41478

American (AMR) AF: 0.275 AC: 4194 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1273 AN: 3472

East Asian (EAS) AF: 0.0708 AC: 367 AN: 5180

South Asian (SAS) AF: 0.389 AC: 1873 AN: 4818

European-Finnish (FIN) AF: 0.310 AC: 3267 AN: 10550

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19604 AN: 67976

Other (OTH) AF: 0.401 AC: 846 AN: 2110

Alfa AF: 0.327 Hom.: 15615

Bravo AF: 0.429

Asia WGS AF: 0.298 AC: 1041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	5.6
DANN	Benign	0.83
PhyloP100		0.62
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs941718; hg19: chr14-23495048;