rs241449

Variant names:

• chr6-32828876-C-A
• rs241449
• NM_001290043.2:c.*30G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32828876-C-A
• chr6-32828876-C-G
• chr6-32828876-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001290043.2(TAP2):​c.*30G>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 0.268 in 1,524,222 control chromosomes in the GnomAD database, including 57,377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5641 hom., cov: 31)
  • Exomes 𝑓: 0.27 (51736 hom.)
• Consequence: TAP2 NM_001290043.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0730
• Publications: 45 publications found

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]

TAP2 Gene-Disease associations (from GenCC):

• MHC class I deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics
• MHC class I deficiency 1

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ENSG00000250264 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 6-32828876-C-A is Benign according to our data. Variant chr6-32828876-C-A is described in ClinVar as Benign. ClinVar VariationId is 403509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290043.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	NM_001290043.2	MANE Select	c.*30G>T		3_prime_UTR	Exon 12 of 12	NP_001276972.1	Q5JNW1
	TAP2	NM_018833.3		c.1932+524G>T		intron	N/A	NP_061313.2	Q9UP03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	ENST00000374897.4	TSL:1 MANE Select	c.*30G>T		3_prime_UTR	Exon 12 of 12	ENSP00000364032.3	Q03519-1
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1932+524G>T		intron	N/A	ENSP00000391806.2	E7ENX8
	TAP2	ENST00000698449.1		c.*30G>T		3_prime_UTR	Exon 13 of 13	ENSP00000513734.1	A0A8V8TNJ0

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40190 AN: 151888 Hom.: 5630 Cov.: 31

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.291

GnomAD2 exomes AF: 0.314 AC: 46386 AN: 147522 AF XY: 0.316

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.355

Gnomad ASJ exome AF: 0.343

Gnomad EAS exome AF: 0.362

Gnomad FIN exome AF: 0.341

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.269 AC: 368871 AN: 1372214 Hom.: 51736 Cov.: 38 AF XY: 0.272 AC XY: 182858 AN XY: 671772

African (AFR) AF: 0.184 AC: 5743 AN: 31232

American (AMR) AF: 0.348 AC: 12332 AN: 35456

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 8700 AN: 24952

East Asian (EAS) AF: 0.354 AC: 12421 AN: 35116

South Asian (SAS) AF: 0.393 AC: 30510 AN: 77614

European-Finnish (FIN) AF: 0.335 AC: 14858 AN: 44374

Middle Eastern (MID) AF: 0.287 AC: 1499 AN: 5226

European-Non Finnish (NFE) AF: 0.251 AC: 266933 AN: 1061444

Other (OTH) AF: 0.279 AC: 15875 AN: 56800

GnomAD4 genome AF: 0.265 AC: 40224 AN: 152008 Hom.: 5641 Cov.: 31 AF XY: 0.273 AC XY: 20275 AN XY: 74286

African (AFR) AF: 0.185 AC: 7665 AN: 41478

American (AMR) AF: 0.329 AC: 5040 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1195 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1880 AN: 5144

South Asian (SAS) AF: 0.399 AC: 1918 AN: 4806

European-Finnish (FIN) AF: 0.344 AC: 3638 AN: 10562

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17835 AN: 67946

Other (OTH) AF: 0.291 AC: 612 AN: 2102

Alfa AF: 0.264 Hom.: 16456

Bravo AF: 0.259

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	MHC class I deficiency (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.7
DANN	Benign	0.73
PhyloP100		-0.073
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs241449; hg19: chr6-32796653;