rs2071536

Variant names:

• chr6-32853670-C-T
• rs2071536
• NM_000593.6:c.-34G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000593.6(TAP1):​c.-34G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,592,482 control chromosomes in the GnomAD database, including 9,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (653 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9190 hom.)
• Consequence: TAP1 NM_000593.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.471
• Publications: 16 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• proteasome-associated autoinflammatory syndrome 3

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 6-32853670-C-T is Benign according to our data. Variant chr6-32853670-C-T is described in ClinVar as Benign. ClinVar VariationId is 403506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP1	NM_000593.6	c.-34G>A		5_prime_UTR_variant	Exon 1 of 11	ENST00000354258.5	NP_000584.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP1	ENST00000354258.5	c.-34G>A		5_prime_UTR_variant	Exon 1 of 11	1	NM_000593.6	ENSP00000346206.5

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12923 AN: 152106 Hom.: 653 Cov.: 32

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.0566

Gnomad ASJ AF: 0.0830

Gnomad EAS AF: 0.0687

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0727

GnomAD2 exomes AF: 0.0986 AC: 19974 AN: 202540 AF XY: 0.105

Gnomad AFR exome AF: 0.0311

Gnomad AMR exome AF: 0.0466

Gnomad ASJ exome AF: 0.0837

Gnomad EAS exome AF: 0.0679

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.0986

GnomAD4 exome AF: 0.110 AC: 158270 AN: 1440258 Hom.: 9190 Cov.: 33 AF XY: 0.111 AC XY: 79262 AN XY: 715142

African (AFR) AF: 0.0314 AC: 1038 AN: 33056

American (AMR) AF: 0.0485 AC: 2060 AN: 42464

Ashkenazi Jewish (ASJ) AF: 0.0848 AC: 2187 AN: 25802

East Asian (EAS) AF: 0.0745 AC: 2888 AN: 38776

South Asian (SAS) AF: 0.131 AC: 11144 AN: 84878

European-Finnish (FIN) AF: 0.118 AC: 5539 AN: 46762

Middle Eastern (MID) AF: 0.0825 AC: 473 AN: 5732

European-Non Finnish (NFE) AF: 0.115 AC: 126877 AN: 1103252

Other (OTH) AF: 0.102 AC: 6064 AN: 59536

GnomAD4 genome AF: 0.0849 AC: 12919 AN: 152224 Hom.: 653 Cov.: 32 AF XY: 0.0852 AC XY: 6342 AN XY: 74418

African (AFR) AF: 0.0328 AC: 1364 AN: 41578

American (AMR) AF: 0.0565 AC: 865 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0830 AC: 288 AN: 3470

East Asian (EAS) AF: 0.0690 AC: 356 AN: 5158

South Asian (SAS) AF: 0.157 AC: 755 AN: 4822

European-Finnish (FIN) AF: 0.117 AC: 1244 AN: 10604

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7678 AN: 67974

Other (OTH) AF: 0.0710 AC: 150 AN: 2112

Alfa AF: 0.0986 Hom.: 232

Bravo AF: 0.0768

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

MHC class I deficiency Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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	-0.87
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		0.47
PromoterAI		-0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2071536; hg19: chr6-32821447; COSMIC: COSV62754041; COSMIC: COSV62754041;