6-32829584-C-T

Position:

• chr6-32829584-C-T

Variant summary

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

The NM_001290043.2(TAP2):​c.1796-48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,610,984 control chromosomes in the GnomAD database, including 60,405 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 0.25 (5342 hom., cov: 32)
  • Exomes 𝑓: 0.27 (55063 hom.)
• Consequence: TAP2 NM_001290043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486

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=-0.82).
• 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.1796-48G>A		intron_variant		ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.1796-48G>A		intron_variant			NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.1796-48G>A		intron_variant		1	NM_001290043.2	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2	c.1796-48G>A		intron_variant		2		ENSP00000391806.2

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38486 AN: 152000 Hom.: 5331 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.275

GnomAD3 exomes AF: 0.298 AC: 73845 AN: 248190 Hom.: 11483 AF XY: 0.301 AC XY: 40416 AN XY: 134146

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.343

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.356

Gnomad SAS exome AF: 0.397

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.284

GnomAD4 exome AF: 0.269 AC: 391934 AN: 1458866 Hom.: 55063 Cov.: 34 AF XY: 0.272 AC XY: 197630 AN XY: 725678

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.350

Gnomad4 EAS exome AF: 0.350

Gnomad4 SAS exome AF: 0.394

Gnomad4 FIN exome AF: 0.339

Gnomad4 NFE exome AF: 0.251

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.253 AC: 38516 AN: 152118 Hom.: 5342 Cov.: 32 AF XY: 0.262 AC XY: 19481 AN XY: 74376

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.275

Alfa AF: 0.265 Hom.: 6409

Bravo AF: 0.245

Asia WGS AF: 0.360 AC: 1251 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	6.5
DANN	Benign	0.64

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: rs241440; hg19: chr6-32797361; COSMIC: COSV66500261; COSMIC: COSV66500261;