Genetic Variant TAP1:c.844+21A>G (chr6-32852088-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000593.6(TAP1):c.844+21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,612,612 control chromosomes in the GnomAD database, including 12,187 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 0.11 ( 1088 hom., cov: 31)

Exomes 𝑓: 0.12 ( 11099 hom. )

Consequence

TAP1
NM_000593.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.279

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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP1	NM_000593.6 link	c.844+21A>G		intron_variant	Intron 3 of 10	ENST00000354258.5	NP_000584.3	Q03518-1A0A0S2Z5A6X5CKB3
TAP1	NM_001292022.2 link	c.241+21A>G		intron_variant	Intron 3 of 10		NP_001278951.1	Q03518B7Z7P4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP1	ENST00000354258.5 link	c.844+21A>G		intron_variant	Intron 3 of 10	1	NM_000593.6	ENSP00000346206.5		Q03518-1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17325

AN:

151840

Hom.:

1076

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0897

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.0908

Gnomad ASJ

AF:

0.0683

Gnomad EAS

AF:

0.213

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.0976

GnomAD3 exomes

AF:

0.138

AC:

33980

AN:

246266

Hom.:

2727

AF XY:

0.140

AC XY:

18800

AN XY:

134312

show subpopulations

Gnomad AFR exome

AF:

0.0907

Gnomad AMR exome

AF:

0.128

Gnomad ASJ exome

AF:

0.0644

Gnomad EAS exome

AF:

0.227

Gnomad SAS exome

AF:

0.210

Gnomad FIN exome

AF:

0.164

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.117

AC:

171314

AN:

1460652

Hom.:

11099

Cov.:

AF XY:

0.120

AC XY:

87353

AN XY:

726660

show subpopulations

Gnomad4 AFR exome

AF:

0.0904

Gnomad4 AMR exome

AF:

0.123

Gnomad4 ASJ exome

AF:

0.0630

Gnomad4 EAS exome

AF:

0.170

Gnomad4 SAS exome

AF:

0.210

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.114

AC:

17364

AN:

151960

Hom.:

1088

Cov.:

AF XY:

0.118

AC XY:

8766

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.0898

Gnomad4 AMR

AF:

0.0918

Gnomad4 ASJ

AF:

0.0683

Gnomad4 EAS

AF:

0.213

Gnomad4 SAS

AF:

0.213

Gnomad4 FIN

AF:

0.163

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.113

Hom.:

2064

Bravo

AF:

0.107

Asia WGS

AF:

0.204

AC:

707

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.0

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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