rs13501

Positions:

• chr6-32825746-G-A
• chr6-32825746-G-C
• chr6-32825746-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290043.2(TAP2):​c.*3160C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,100 control chromosomes in the GnomAD database, including 10,064 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 0.36 (10057 hom., cov: 32)
  • Exomes 𝑓: 0.21 (7 hom.)
• Consequence: TAP2 NM_001290043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

Genes affected

TAP2 (HGNC:44): (transporter 2, 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. This gene is located 7 kb telomeric to gene family member ABCB2. The protein encoded by this gene is involved in antigen presentation. This protein forms a heterodimer with ABCB2 in order to transport peptides from the cytoplasm to the endoplasmic reticulum. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Alternative splicing of this gene produces products which differ in peptide selectivity and level of restoration of surface expression of MHC class I molecules. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.*3160C>T		3_prime_UTR_variant	12/12	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.1933-3428C>T		intron_variant			NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.*3160C>T		3_prime_UTR_variant	12/12	1	NM_001290043.2	ENSP00000364032	A2

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54836 AN: 151826 Hom.: 10050 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.205 AC: 32 AN: 156 Hom.: 7 Cov.: 0 AF XY: 0.195 AC XY: 16 AN XY: 82

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.167

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.361 AC: 54879 AN: 151944 Hom.: 10057 Cov.: 32 AF XY: 0.370 AC XY: 27495 AN XY: 74286

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.368

Alfa AF: 0.333 Hom.: 1574

Bravo AF: 0.359

Asia WGS AF: 0.392 AC: 1365 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.53
DANN	Benign	0.43

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

Other links and lift over

dbSNP: rs13501; hg19: chr6-32793523;