Genetic Variant TAPBP:n.1101T>A (chr6-33304764-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000480730.5(TAPBP):n.1101T>A 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 0.477 in 1,275,234 control chromosomes in the GnomAD database, including 151,757 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 0.40 ( 14098 hom., cov: 32)

Exomes 𝑓: 0.49 ( 137659 hom. )

Consequence

TAPBP
ENST00000480730.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.758

Publications

11 publications found

Variant links:

Genes affected

TAPBP (HGNC:11566): (TAP binding protein) This gene encodes a transmembrane glycoprotein which mediates interaction between newly assembled major histocompatibility complex (MHC) class I molecules and the transporter associated with antigen processing (TAP), which is required for the transport of antigenic peptides across the endoplasmic reticulum membrane. This interaction is essential for optimal peptide loading on the MHC class I molecule. Up to four complexes of MHC class I and this protein may be bound to a single TAP molecule. This protein contains a C-terminal double-lysine motif (KKKAE) known to maintain membrane proteins in the endoplasmic reticulum. This gene lies within the major histocompatibility complex on chromosome 6. Alternative splicing results in three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

TAPBP Gene-Disease associations (from GenCC):

MHC class I deficiency
Inheritance: AR Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

TAPBP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAPBP	NM_003190.5 link	c.869-126T>A		intron_variant	Intron 4 of 7	ENST00000434618.7	NP_003181.3	O15533-1A0A024RCT1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAPBP	ENST00000434618.7 link	c.869-126T>A		intron_variant	Intron 4 of 7	1	NM_003190.5	ENSP00000395701.2		O15533-1

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60740

AN:

151850

Hom.:

14099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.492

Gnomad EAS

AF:

0.359

Gnomad SAS

AF:

0.607

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.396

GnomAD4 exome

AF:

0.488

AC:

547818

AN:

1123266

Hom.:

137659

Cov.:

AF XY:

0.493

AC XY:

274622

AN XY:

557286

show subpopulations

African (AFR)

AF:

0.130

AC:

3383

AN:

25942

American (AMR)

AF:

0.474

AC:

12471

AN:

26300

Ashkenazi Jewish (ASJ)

AF:

0.490

AC:

8951

AN:

18264

East Asian (EAS)

AF:

0.337

AC:

12562

AN:

37324

South Asian (SAS)

AF:

0.607

AC:

38292

AN:

63134

European-Finnish (FIN)

AF:

0.521

AC:

18367

AN:

35278

Middle Eastern (MID)

AF:

0.431

AC:

1430

AN:

3318

European-Non Finnish (NFE)

AF:

0.496

AC:

429407

AN:

865506

Other (OTH)

AF:

0.476

AC:

22955

AN:

48200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

14338

28677

43015

57354

71692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11912

23824

35736

47648

59560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.400

AC:

60747

AN:

151968

Hom.:

14098

Cov.:

AF XY:

0.405

AC XY:

30112

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.149

AC:

6181

AN:

41438

American (AMR)

AF:

0.465

AC:

7105

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.492

AC:

1704

AN:

3466

East Asian (EAS)

AF:

0.359

AC:

1853

AN:

5166

South Asian (SAS)

AF:

0.607

AC:

2929

AN:

4828

European-Finnish (FIN)

AF:

0.523

AC:

5526

AN:

10568

Middle Eastern (MID)

AF:

0.384

AC:

113

AN:

294

European-Non Finnish (NFE)

AF:

0.503

AC:

34175

AN:

67924

Other (OTH)

AF:

0.397

AC:

837

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1709

3417

5126

6834

8543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.445

Hom.:

2007

Bravo

AF:

0.379

Asia WGS

AF:

0.448

AC:

1559

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.76

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over