6-32844751-C-T

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.296C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 309,492 control chromosomes in the GnomAD database, including 5,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1941 hom., cov: 32)
  • Exomes 𝑓: 0.18 (3159 hom.)
• Consequence: PSMB8-AS1 NR_037173.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.84

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=-0.76).
• BP6: Variant 6-32844751-C-T is Benign according to our data. Variant chr6-32844751-C-T is described in ClinVar as [Benign]. Clinvar id is 1275279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMB8-AS1	NR_037173.1	n.296C>T		non_coding_transcript_exon_variant	2/3
PSMB8-AS1	NR_037174.1	n.189+477C>T		intron_variant, non_coding_transcript_variant
PSMB8-AS1	NR_037175.1	n.190-59C>T		intron_variant, non_coding_transcript_variant
PSMB8-AS1	NR_037176.1	n.189+477C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB8-AS1	ENST00000453426.2	n.189+477C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21850 AN: 152114 Hom.: 1940 Cov.: 32

Gnomad AFR AF: 0.0469

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.184 AC: 28950 AN: 157260 Hom.: 3159 Cov.: 0 AF XY: 0.189 AC XY: 15647 AN XY: 82584

Gnomad4 AFR exome AF: 0.0471

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.301

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.144 AC: 21861 AN: 152232 Hom.: 1941 Cov.: 32 AF XY: 0.148 AC XY: 10992 AN XY: 74414

Gnomad4 AFR AF: 0.0468

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.143

Alfa AF: 0.165 Hom.: 4025

Bravo AF: 0.140

Asia WGS AF: 0.285 AC: 989 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 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.025
Dann	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071463; hg19: chr6-32812528;