rs2071541

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.689

Publications

35 publications found

Variant links:

Genes affected

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

PSMB8-AS1 links:

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]

PSMB9 links:

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

TAP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 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 rank	MANE	Protein	UniProt
TAP1	NM_000593.6 link	c.*498T>C		downstream_gene_variant		ENST00000354258.5	NP_000584.3	Q03518-1A0A0S2Z5A6X5CKB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP1	ENST00000354258.5 link	c.*498T>C		downstream_gene_variant		1	NM_000593.6	ENSP00000346206.5		Q03518-1

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17425

AN:

152106

Hom.:

1053

Cov.:

show subpopulations

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

show subpopulations

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:

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:

AN:

168

European-Non Finnish (NFE)

AF:

0.108

AC:

4150

AN:

38512

Other (OTH)

AF:

0.0964

AC:

276

AN:

2864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

314

629

943

1258

1572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.115

AC:

17453

AN:

152224

Hom.:

1062

Cov.:

AF XY:

0.118

AC XY:

8786

AN XY:

74440

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.126

AC:

8535

AN:

68004

Other (OTH)

AF:

0.0999

AC:

211

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

813

1626

2439

3252

4065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

LINK: link

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.4

(source)

DANN

Benign

0.53

PhyloP100

0.69

PromoterAI

0.0022

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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rs2071541

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over