6-32845024-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NR_037173.1(PSMB8-AS1):n.415+154G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0869 in 152,250 control chromosomes in the GnomAD database, including 788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.087 (788 hom., cov: 32)
• Consequence: PSMB8-AS1 NR_037173.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.176

Genes affected

PSMB8-AS1 (HGNC:39758): (PSMB8 antisense RNA 1 (head to head))

PSMB9 (HGNC:9546): (proteasome 20S subunit beta 9) 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 located in the class II region of the MHC (major histocompatibility complex). Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 1 (proteasome beta 6 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-32845024-G-A is Benign according to our data. Variant chr6-32845024-G-A is described in ClinVar as [Benign]. Clinvar id is 1251687.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMB8-AS1	NR_037173.1	n.415+154G>A		intron_variant, non_coding_transcript_variant
PSMB8-AS1	NR_037174.1	n.190-306G>A		intron_variant, non_coding_transcript_variant
PSMB8-AS1	NR_037175.1	n.250+154G>A		intron_variant, non_coding_transcript_variant
PSMB8-AS1	NR_037176.1	n.190-394G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB8-AS1	ENST00000453426.2	n.190-394G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0866 AC: 13182 AN: 152132 Hom.: 778 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0705

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.0373

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0568

Gnomad OTH AF: 0.0817

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

GnomAD4 genome AF: 0.0869 AC: 13226 AN: 152250 Hom.: 788 Cov.: 32 AF XY: 0.0848 AC XY: 6317 AN XY: 74466

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0704

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.0395

Gnomad4 FIN AF: 0.0373

Gnomad4 NFE AF: 0.0567

Gnomad4 OTH AF: 0.0808

Alfa AF: 0.0745 Hom.: 76

Bravo AF: 0.0931

Asia WGS AF: 0.0470 AC: 165 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.9
Dann	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs113215190; hg19: chr6-32812801;