rs241456

chr6-32828188-G-Achr6-32828188-G-Cchr6-32828188-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001290043.2(TAP2):c.*718C>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 0.238 in 882,234 control chromosomes in the GnomAD database, including 25,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5620 hom., cov: 31)
  • Exomes 𝑓: 0.23 (20188 hom.)
• Consequence: TAP2 NM_001290043.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0280

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-32828188-G-A is Benign according to our data. Variant chr6-32828188-G-A is described in ClinVar as [Benign]. Clinvar id is 1296950.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	UniProt
TAP2	NM_001290043.2	c.*718C>T		3_prime_UTR_variant	12/12	ENST00000374897.4
TAP2	NM_018833.3	c.1932+1212C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP2	ENST00000374897.4	c.*718C>T		3_prime_UTR_variant	12/12	1	NM_001290043.2	A2

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40110 AN: 151818 Hom.: 5610 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.233 AC: 169982 AN: 730298 Hom.: 20188 Cov.: 10 AF XY: 0.233 AC XY: 79046 AN XY: 339152

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.295

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.388

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.264 AC: 40144 AN: 151936 Hom.: 5620 Cov.: 31 AF XY: 0.273 AC XY: 20239 AN XY: 74230

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.289

Alfa AF: 0.267 Hom.: 8021

Bravo AF: 0.258

Asia WGS AF: 0.357 AC: 1243 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 20, 2019

This variant is associated with the following publications: (PMID: 29205500) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.8
Dann	Benign	0.66

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: rs241456; hg19: chr6-32795965;