Variant rs2071538 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0940

Variant links:

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]

TAP1 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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TAP1	NM_000593.6 linkuse as main transcript	c.1050+43C>T		intron_variant		ENST00000354258.5
TAP1	NM_001292022.2 linkuse as main transcript	c.447+43C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP1	ENST00000354258.5 linkuse as main transcript	c.1050+43C>T		intron_variant		1	NM_000593.6	P1	Q03518-1

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25907

AN:

151946

Hom.:

2960

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.184

AC:

44993

AN:

244944

Hom.:

5023

AF XY:

0.187

AC XY:

24982

AN XY:

133638

show subpopulations

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 SAS exome

AF:

0.138

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.:

AF XY:

0.213

AC XY:

149471

AN XY:

702106

show subpopulations

Gnomad4 AFR exome

AF:

0.0327

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.207

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.141

Gnomad4 FIN exome

AF:

0.311

Gnomad4 NFE exome

AF:

0.229

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.170

AC:

25911

AN:

152064

Hom.:

2960

Cov.:

AF XY:

0.175

AC XY:

13007

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0386

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.209

Gnomad4 EAS

AF:

0.0539

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.319

Gnomad4 NFE

AF:

0.236

Gnomad4 OTH

AF:

0.139

Alfa

AF:

0.215

Hom.:

7243

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over