6-32844876-TTG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NR_037173.1(PSMB8-AS1):n.415+9_415+10del variant causes a splice region, intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 184,810 control chromosomes in the GnomAD database, including 198 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (195 hom., cov: 31)
  • Exomes 𝑓: 0.0031 (3 hom.)
• Consequence: PSMB8-AS1 NR_037173.1 splice_region, intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.276

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 -10 ACMG points.

• BP6: Variant 6-32844876-TTG-T is Benign according to our data. Variant chr6-32844876-TTG-T is described in ClinVar as [Benign]. Clinvar id is 1248040.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMB8-AS1	NR_037173.1	n.415+9_415+10del		splice_region_variant, intron_variant, non_coding_transcript_variant
PSMB8-AS1	NR_037174.1	n.190-451_190-450del		intron_variant, non_coding_transcript_variant
PSMB8-AS1	NR_037175.1	n.250+9_250+10del		splice_region_variant, intron_variant, non_coding_transcript_variant
PSMB8-AS1	NR_037176.1	n.190-539_190-538del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB8-AS1	ENST00000453426.2	n.190-539_190-538del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0294 AC: 4470 AN: 152096 Hom.: 196 Cov.: 31

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.00307 AC: 100 AN: 32596 Hom.: 3 AF XY: 0.00221 AC XY: 39 AN XY: 17642

Gnomad4 AFR exome AF: 0.0724

Gnomad4 AMR exome AF: 0.00804

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000168

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000171

Gnomad4 OTH exome AF: 0.00481

GnomAD4 genome AF: 0.0294 AC: 4477 AN: 152214 Hom.: 195 Cov.: 31 AF XY: 0.0286 AC XY: 2129 AN XY: 74416

Gnomad4 AFR AF: 0.0986

Gnomad4 AMR AF: 0.0192

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0228 Hom.: 17

Bravo AF: 0.0343

Asia WGS AF: 0.00404 AC: 14 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 25, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs143782064; hg19: chr6-32812653;