chr6-32845081-A-G

Position:

• chr6-32845081-A-G

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+211A>G 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 0.117 in 217,142 control chromosomes in the GnomAD database, including 1,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1062 hom., cov: 32)
  • Exomes 𝑓: 0.12 (636 hom.)
• Consequence: PSMB8-AS1 NR_037173.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.689

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=-0.9).
• BP6: Variant 6-32845081-A-G is Benign according to our data. Variant chr6-32845081-A-G is described in ClinVar as [Benign]. Clinvar id is 1253267.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMB8-AS1	NR_037173.1	n.415+211A>G		intron_variant, non_coding_transcript_variant
PSMB8-AS1	NR_037174.1	n.190-249A>G		intron_variant, non_coding_transcript_variant
PSMB8-AS1	NR_037175.1	n.250+211A>G		intron_variant, non_coding_transcript_variant
PSMB8-AS1	NR_037176.1	n.190-337A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB8-AS1	ENST00000453426.2	n.190-337A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17425 AN: 152106 Hom.: 1053 Cov.: 32

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.0938

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0962

GnomAD4 exome AF: 0.121 AC: 7870 AN: 64918 Hom.: 636 AF XY: 0.125 AC XY: 4433 AN XY: 35416

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.0317

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.0964

GnomAD4 genome AF: 0.115 AC: 17453 AN: 152224 Hom.: 1062 Cov.: 32 AF XY: 0.118 AC XY: 8786 AN XY: 74440

Gnomad4 AFR AF: 0.0777

Gnomad4 AMR AF: 0.0949

Gnomad4 ASJ AF: 0.0539

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.0999

Alfa AF: 0.121 Hom.: 2159

Bravo AF: 0.107

Asia WGS AF: 0.180 AC: 626 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	-0.90
CADD	Benign	7.4
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2071541; hg19: chr6-32812858;