ENST00000395330.5:c.-10+750G>A

Variant names:

• chr6-32845024-G-A
• rs113215190
• ENST00000395330.6:c.-10+750G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000395330.6(PSMB9):​c.-10+750G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0869 in 152,250 control chromosomes in the GnomAD database, including 788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.087 (788 hom., cov: 32)
• Consequence: PSMB9 ENST00000395330.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.176
• Publications: 6 publications found

Genes affected

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]

PSMB8-AS1 (HGNC:39758): (PSMB8 antisense RNA 1 (head to head))

TAP1 (HGNC:43): (transporter 1, ATP binding cassette subfamily B member) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is involved in the pumping of degraded cytosolic peptides across the endoplasmic reticulum into the membrane-bound compartment where class I molecules assemble. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

TAP1 Gene-Disease associations (from GenCC):

• MHC class I deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• MHC class I deficiency 1

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-32845024-G-A is Benign according to our data. Variant chr6-32845024-G-A is described in ClinVar as Benign. ClinVar VariationId is 1251687.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000395330.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB8-AS1	NR_037173.1		n.415+154G>A		intron	N/A
	PSMB8-AS1	NR_037174.1		n.190-306G>A		intron	N/A
	PSMB8-AS1	NR_037175.1		n.250+154G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB9	ENST00000395330.6	TSL:3	c.-10+750G>A		intron	N/A	ENSP00000378739.1	A2ACR1
	PSMB9	ENST00000414474.5	TSL:5	c.-10+154G>A		intron	N/A	ENSP00000394363.1	A2ACR0
	PSMB8-AS1	ENST00000666376.1		n.906G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0866 AC: 13182 AN: 152132 Hom.: 778 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0705

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.0373

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0568

Gnomad OTH AF: 0.0817

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

GnomAD4 genome AF: 0.0869 AC: 13226 AN: 152250 Hom.: 788 Cov.: 32 AF XY: 0.0848 AC XY: 6317 AN XY: 74466

African (AFR) AF: 0.166 AC: 6874 AN: 41510

American (AMR) AF: 0.0704 AC: 1076 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3472

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5180

South Asian (SAS) AF: 0.0395 AC: 191 AN: 4834

European-Finnish (FIN) AF: 0.0373 AC: 396 AN: 10620

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0567 AC: 3860 AN: 68020

Other (OTH) AF: 0.0808 AC: 171 AN: 2116

Alfa AF: 0.0774 Hom.: 80

Bravo AF: 0.0931

Asia WGS AF: 0.0470 AC: 165 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.54
PhyloP100		0.18
PromoterAI		0.0021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs113215190; hg19: chr6-32812801;