rs2071538

Variant names:

• chr6-32850901-G-A
• rs2071538
• NM_000593.6:c.1050+43C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32850901-G-A
• chr6-32850901-G-C
• chr6-32850901-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000593.6(TAP1):​c.1050+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,556,828 control chromosomes in the GnomAD database, including 37,059 homozygotes. 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: 𝑓 0.17 (2960 hom., cov: 31)
  • Exomes 𝑓: 0.21 (34099 hom.)
• Consequence: TAP1 NM_000593.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 39 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP1	NM_000593.6	c.1050+43C>T		intron_variant	Intron 4 of 10	ENST00000354258.5	NP_000584.3
TAP1	NM_001292022.2	c.447+43C>T		intron_variant	Intron 4 of 10		NP_001278951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP1	ENST00000354258.5	c.1050+43C>T		intron_variant	Intron 4 of 10	1	NM_000593.6	ENSP00000346206.5

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25907 AN: 151946 Hom.: 2960 Cov.: 31

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0540

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.141

GnomAD2 exomes AF: 0.184 AC: 44993 AN: 244944 AF XY: 0.187

Gnomad AFR exome AF: 0.0336

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.0286

Gnomad FIN exome AF: 0.315

Gnomad NFE exome AF: 0.229

Gnomad OTH exome AF: 0.184

GnomAD4 exome AF: 0.214 AC: 300195 AN: 1404764 Hom.: 34099 Cov.: 26 AF XY: 0.213 AC XY: 149471 AN XY: 702106

African (AFR) AF: 0.0327 AC: 1050 AN: 32090

American (AMR) AF: 0.143 AC: 6393 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5348 AN: 25808

East Asian (EAS) AF: 0.105 AC: 4149 AN: 39426

South Asian (SAS) AF: 0.141 AC: 11964 AN: 84920

European-Finnish (FIN) AF: 0.311 AC: 16268 AN: 52298

Middle Eastern (MID) AF: 0.155 AC: 659 AN: 4248

European-Non Finnish (NFE) AF: 0.229 AC: 243332 AN: 1062964

Other (OTH) AF: 0.189 AC: 11032 AN: 58374

GnomAD4 genome AF: 0.170 AC: 25911 AN: 152064 Hom.: 2960 Cov.: 31 AF XY: 0.175 AC XY: 13007 AN XY: 74324

African (AFR) AF: 0.0386 AC: 1602 AN: 41512

American (AMR) AF: 0.179 AC: 2740 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3468

East Asian (EAS) AF: 0.0539 AC: 279 AN: 5176

South Asian (SAS) AF: 0.130 AC: 626 AN: 4808

European-Finnish (FIN) AF: 0.319 AC: 3361 AN: 10552

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.236 AC: 16038 AN: 67956

Other (OTH) AF: 0.139 AC: 294 AN: 2114

Alfa AF: 0.206 Hom.: 14527

Bravo AF: 0.151

Asia WGS AF: 0.0830 AC: 293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.6
DANN	Benign	0.74
PhyloP100		0.094
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: rs2071538; hg19: chr6-32818678; COSMIC: COSV62754545; COSMIC: COSV62754545;