chr6-32845081-A-G

Variant names:

• chr6-32845081-A-G
• rs2071541
• ENST00000666376.1:n.963A>G

Variant summary

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

The ENST00000666376.1(PSMB8-AS1):​n.963A>G variant causes a non coding transcript exon 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 ENST00000666376.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.689
• Publications: 35 publications found

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]

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: Orphanet, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• MHC class I deficiency 1

  Inheritance: AR Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000666376.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB8-AS1	NR_037173.1		n.415+211A>G		intron	N/A
	PSMB8-AS1	NR_037174.1		n.190-249A>G		intron	N/A
	PSMB8-AS1	NR_037175.1		n.250+211A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB8-AS1	ENST00000666376.1		n.963A>G		non_coding_transcript_exon	Exon 1 of 1
	PSMB9	ENST00000395330.6	TSL:3	c.-10+807A>G		intron	N/A	ENSP00000378739.1
	PSMB9	ENST00000414474.5	TSL:5	c.-10+211A>G		intron	N/A	ENSP00000394363.1

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

African (AFR) AF: 0.0714 AC: 110 AN: 1540

American (AMR) AF: 0.129 AC: 483 AN: 3752

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 39 AN: 1232

East Asian (EAS) AF: 0.138 AC: 471 AN: 3420

South Asian (SAS) AF: 0.179 AC: 2106 AN: 11734

European-Finnish (FIN) AF: 0.131 AC: 223 AN: 1696

Middle Eastern (MID) AF: 0.0714 AC: 12 AN: 168

European-Non Finnish (NFE) AF: 0.108 AC: 4150 AN: 38512

Other (OTH) AF: 0.0964 AC: 276 AN: 2864

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

African (AFR) AF: 0.0777 AC: 3226 AN: 41534

American (AMR) AF: 0.0949 AC: 1451 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 187 AN: 3470

East Asian (EAS) AF: 0.155 AC: 801 AN: 5180

South Asian (SAS) AF: 0.203 AC: 977 AN: 4824

European-Finnish (FIN) AF: 0.176 AC: 1863 AN: 10598

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8535 AN: 68004

Other (OTH) AF: 0.0999 AC: 211 AN: 2112

Alfa AF: 0.118 Hom.: 3464

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

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.4
DANN	Benign	0.53
PhyloP100		0.69
PromoterAI		0.0022	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: rs2071541; hg19: chr6-32812858;