6-32845139-T-C

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+269T>C 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 0.599 in 255,686 control chromosomes in the GnomAD database, including 46,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (28925 hom., cov: 33)
  • Exomes 𝑓: 0.58 (17945 hom.)
• Consequence: PSMB8-AS1 NR_037173.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.98

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=-0.98).
• BP6: Variant 6-32845139-T-C is Benign according to our data. Variant chr6-32845139-T-C is described in ClinVar as [Benign]. Clinvar id is 1271041.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMB8-AS1	NR_037173.1	n.415+269T>C		intron_variant, non_coding_transcript_variant
PSMB8-AS1	NR_037174.1	n.190-191T>C		intron_variant, non_coding_transcript_variant
PSMB8-AS1	NR_037175.1	n.250+269T>C		intron_variant, non_coding_transcript_variant
PSMB8-AS1	NR_037176.1	n.190-279T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB8-AS1	ENST00000453426.2	n.190-279T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.612 AC: 93082 AN: 151972 Hom.: 28892 Cov.: 33

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.578 AC: 59869 AN: 103596 Hom.: 17945 AF XY: 0.580 AC XY: 32388 AN XY: 55814

Gnomad4 AFR exome AF: 0.687

Gnomad4 AMR exome AF: 0.597

Gnomad4 ASJ exome AF: 0.533

Gnomad4 EAS exome AF: 0.657

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.545

Gnomad4 NFE exome AF: 0.560

Gnomad4 OTH exome AF: 0.590

GnomAD4 genome AF: 0.613 AC: 93164 AN: 152090 Hom.: 28925 Cov.: 33 AF XY: 0.610 AC XY: 45323 AN XY: 74348

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.604

Alfa AF: 0.585 Hom.: 12401

Bravo AF: 0.618

Asia WGS AF: 0.628 AC: 2186 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.83
Dann	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071540; hg19: chr6-32812916;