rs941717

Variant names:

• chr14-23025778-T-C
• rs941717
• ENST00000926152.1:c.*34+277A>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+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
• Publications: 6 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=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000555895.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB5	NM_002797.5	MANE Select	c.*311A>G		downstream_gene	N/A	NP_002788.1	P28074-1
	PSMB5	NM_001144932.3		c.*576A>G		downstream_gene	N/A	NP_001138404.1	P28074-2
	PSMB5	NM_001130725.1		c.*311A>G		downstream_gene	N/A	NP_001124197.1	P28074-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB5	ENST00000926152.1		c.*34+277A>G		intron	N/A	ENSP00000596210.1
	PSMB5	ENST00000926153.1		c.*47+264A>G		intron	N/A	ENSP00000596211.1
	PSMB5	ENST00000555895.5	TSL:3	c.349+7590A>G		intron	N/A	ENSP00000451816.1	H0YJM8

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

African (AFR) AF: 0.868 AC: 14475 AN: 16684

American (AMR) AF: 0.318 AC: 3120 AN: 9800

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 5105 AN: 10186

East Asian (EAS) AF: 0.184 AC: 2927 AN: 15884

South Asian (SAS) AF: 0.502 AC: 20822 AN: 41446

European-Finnish (FIN) AF: 0.440 AC: 5344 AN: 12150

Middle Eastern (MID) AF: 0.534 AC: 1085 AN: 2030

European-Non Finnish (NFE) AF: 0.457 AC: 286986 AN: 627904

Other (OTH) AF: 0.465 AC: 14172 AN: 30454

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

African (AFR) AF: 0.845 AC: 35068 AN: 41524

American (AMR) AF: 0.374 AC: 5713 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1710 AN: 3470

East Asian (EAS) AF: 0.194 AC: 1003 AN: 5178

South Asian (SAS) AF: 0.505 AC: 2435 AN: 4820

European-Finnish (FIN) AF: 0.443 AC: 4685 AN: 10576

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.462 AC: 31373 AN: 67966

Other (OTH) AF: 0.528 AC: 1113 AN: 2108

Alfa AF: 0.532 Hom.: 3874

Bravo AF: 0.554

Asia WGS AF: 0.394 AC: 1375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Benign	0.73
PhyloP100		2.2
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: rs941717; hg19: chr14-23494987;