6-32843606-A-G

Position:

• chr6-32843606-A-G

Variant summary

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

The NM_148919.4(PSMB8):​c.147+244T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,006 control chromosomes in the GnomAD database, including 12,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.40 (12527 hom., cov: 32)
• Consequence: PSMB8 NM_148919.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.311

Genes affected

PSMB8 (HGNC:9545): (proteasome 20S subunit beta 8) 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 3 (proteasome beta 5 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit. Two alternative transcripts encoding two isoforms have been identified; both isoforms are processed to yield the same mature subunit. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-32843606-A-G is Benign according to our data. Variant chr6-32843606-A-G is described in ClinVar as [Benign]. Clinvar id is 1253407.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMB8	NM_148919.4	c.147+244T>C		intron_variant		ENST00000374882.8
PSMB8	NM_004159.5	c.136-517T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMB8	ENST00000374882.8	c.147+244T>C		intron_variant		1	NM_148919.4	P1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61146 AN: 151888 Hom.: 12528 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.402 AC: 61150 AN: 152006 Hom.: 12527 Cov.: 32 AF XY: 0.398 AC XY: 29585 AN XY: 74284

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.406

Alfa AF: 0.420 Hom.: 14059

Bravo AF: 0.403

Asia WGS AF: 0.398 AC: 1384 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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6924102; hg19: chr6-32811383;