6-32828367-A-G

Position:

• chr6-32828367-A-G

Variant summary

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

The NM_001290043.2(TAP2):​c.*539T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 985,118 control chromosomes in the GnomAD database, including 32,331 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 0.26 (5627 hom., cov: 31)
  • Exomes 𝑓: 0.25 (26704 hom.)
• Consequence: TAP2 NM_001290043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397

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]

ENSG00000250264 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.*539T>C		3_prime_UTR_variant	12/12	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.1932+1033T>C		intron_variant			NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.*539T>C		3_prime_UTR_variant	12/12	1	NM_001290043.2	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2	c.1932+1033T>C		intron_variant		2		ENSP00000391806.2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40162 AN: 151834 Hom.: 5617 Cov.: 31

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.250 AC: 208193 AN: 833166 Hom.: 26704 Cov.: 30 AF XY: 0.250 AC XY: 96107 AN XY: 384802

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.352

Gnomad4 SAS exome AF: 0.411

Gnomad4 FIN exome AF: 0.337

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.265 AC: 40195 AN: 151952 Hom.: 5627 Cov.: 31 AF XY: 0.273 AC XY: 20263 AN XY: 74258

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.289

Alfa AF: 0.263 Hom.: 4123

Bravo AF: 0.259

Asia WGS AF: 0.358 AC: 1244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.71

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: rs241454; hg19: chr6-32796144;