rs2071540

Variant names:

• chr6-32845139-T-A
• rs2071540
• ENST00000395330.6:c.-10+865T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-32845139-T-A
• chr6-32845139-T-C
• chr6-32845139-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000395330.6(PSMB9):​c.-10+865T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PSMB9 ENST00000395330.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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+269T>A		intron	N/A
	PSMB8-AS1	NR_037174.1		n.190-191T>A		intron	N/A
	PSMB8-AS1	NR_037175.1		n.250+269T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB9	ENST00000395330.6	TSL:3	c.-10+865T>A		intron	N/A	ENSP00000378739.1	A2ACR1
	PSMB9	ENST00000414474.5	TSL:5	c.-10+269T>A		intron	N/A	ENSP00000394363.1	A2ACR0
	PSMB8-AS1	ENST00000666376.1		n.1021T>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 103928 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 56002

African (AFR) AF: 0.00 AC: 0 AN: 3114

American (AMR) AF: 0.00 AC: 0 AN: 4470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2402

East Asian (EAS) AF: 0.00 AC: 0 AN: 4894

South Asian (SAS) AF: 0.00 AC: 0 AN: 18090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 340

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62274

Other (OTH) AF: 0.00 AC: 0 AN: 4964

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.70
DANN	Benign	0.50
PhyloP100		-3.0
PromoterAI		-0.030	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2071540; hg19: chr6-32812916;