rs228275

Positions:

• chr17-38754572-C-T

Variant summary

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

The NM_002795.4(PSMB3):​c.188+1238C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,112 control chromosomes in the GnomAD database, including 8,702 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 0.32 (8702 hom., cov: 32)
• Consequence: PSMB3 NM_002795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601

Genes affected

PSMB3 (HGNC:9540): (proteasome 20S subunit beta 3) 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. The 26 S proteasome may be involved in trinucleotide repeat expansion, a phenomenon which is associated with many hereditary neurological diseases. Pseudogenes have been identified on chromosomes 2 and 12. Alternative splicing results in multiple transcript variants [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMB3	NM_002795.4	c.188+1238C>T		intron_variant		ENST00000619426.5
PSMB3	NR_104194.2	n.274+1238C>T		intron_variant, non_coding_transcript_variant
PSMB3	NR_104195.2	n.274+1238C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB3	ENST00000619426.5	c.188+1238C>T		intron_variant		1	NM_002795.4	P1
PSMB3	ENST00000610434.4	c.179+1238C>T		intron_variant		3
PSMB3	ENST00000613870.4	c.188+1238C>T		intron_variant, NMD_transcript_variant		3
PSMB3	ENST00000620309.4	c.188+1238C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48733 AN: 151994 Hom.: 8705 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.311

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.321 AC: 48763 AN: 152112 Hom.: 8702 Cov.: 32 AF XY: 0.325 AC XY: 24170 AN XY: 74348

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.648

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.313

Alfa AF: 0.344 Hom.: 18416

Bravo AF: 0.325

Asia WGS AF: 0.463 AC: 1611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.78

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: rs228275; hg19: chr17-36910825;