rs241451

chr6-32828703-T-C

Variant summary

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

The NM_001290043.2(TAP2):c.*203A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 692,078 control chromosomes in the GnomAD database, including 44,773 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 0.34 (7448 hom., cov: 21)
  • Exomes 𝑓: 0.44 (37325 hom.)
• Consequence: TAP2 NM_001290043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.26

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAP2	NM_001290043.2	c.*203A>G		3_prime_UTR_variant	12/12	ENST00000374897.4
TAP2	NM_018833.3	c.1932+697A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP2	ENST00000374897.4	c.*203A>G		3_prime_UTR_variant	12/12	1	NM_001290043.2	A2

Frequencies

GnomAD3 genomes AF: 0.344 AC: 45533 AN: 132364 Hom.: 7441 Cov.: 21

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.442 AC: 247577 AN: 559640 Hom.: 37325 Cov.: 10 AF XY: 0.440 AC XY: 114710 AN XY: 260530

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.470

Gnomad4 EAS exome AF: 0.356

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.447

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.344 AC: 45564 AN: 132438 Hom.: 7448 Cov.: 21 AF XY: 0.354 AC XY: 22458 AN XY: 63408

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.344

Alfa AF: 0.322 Hom.: 14031

Bravo AF: 0.320

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.82
Dann	Benign	0.45

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: rs241451; hg19: chr6-32796480; COSMIC: COSV66500441; COSMIC: COSV66500441;