rs16870907

chr6-32822030-C-T

Variant summary

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

The NM_018833.3(TAP2):c.*259G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 473,794 control chromosomes in the GnomAD database, including 1,721 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 0.10 (1222 hom., cov: 31)
  • Exomes 𝑓: 0.048 (499 hom.)
• Consequence: TAP2 NM_018833.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.656

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAP2	NM_018833.3	c.*259G>A		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP2	ENST00000652259.1	c.*259G>A		3_prime_UTR_variant	12/12

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15558 AN: 152016 Hom.: 1219 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.0635

Gnomad ASJ AF: 0.0289

Gnomad EAS AF: 0.0343

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.0858

GnomAD4 exome AF: 0.0480 AC: 15453 AN: 321660 Hom.: 499 Cov.: 0 AF XY: 0.0440 AC XY: 7365 AN XY: 167448

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.0445

Gnomad4 ASJ exome AF: 0.0217

Gnomad4 EAS exome AF: 0.0416

Gnomad4 SAS exome AF: 0.0108

Gnomad4 FIN exome AF: 0.0752

Gnomad4 NFE exome AF: 0.0465

Gnomad4 OTH exome AF: 0.0516

GnomAD4 genome AF: 0.102 AC: 15585 AN: 152134 Hom.: 1222 Cov.: 31 AF XY: 0.102 AC XY: 7609 AN XY: 74394

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.0634

Gnomad4 ASJ AF: 0.0289

Gnomad4 EAS AF: 0.0343

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0547

Gnomad4 OTH AF: 0.0882

Alfa AF: 0.0669 Hom.: 434

Bravo AF: 0.106

Asia WGS AF: 0.0360 AC: 128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	8.1
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs16870907; hg19: chr6-32789807;