rs16870907

Variant names:

• chr6-32822030-C-T
• rs16870907
• ENST00000452392.2:c.1933-5078G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000452392.2(ENSG00000250264):​c.1933-5078G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 473,794 control chromosomes in the GnomAD database, including 1,721 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 0.10 (1222 hom., cov: 31)
  • Exomes 𝑓: 0.048 (499 hom.)
• Consequence: ENSG00000250264 ENST00000452392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.656
• Publications: 10 publications found

Genes affected

ENSG00000250264 (HGNC:):

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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_018833.3	c.*259G>A		3_prime_UTR_variant	Exon 12 of 12		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000250264	ENST00000452392.2	c.1933-5078G>A		intron_variant	Intron 11 of 14	2		ENSP00000391806.2
TAP2	ENST00000652259.1	c.*259G>A		3_prime_UTR_variant	Exon 12 of 12			ENSP00000498827.1
ENSG00000307274	ENST00000824890.1	n.79+1150C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15558 AN: 152016 Hom.: 1219 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.0635

Gnomad ASJ AF: 0.0289

Gnomad EAS AF: 0.0343

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.0858

GnomAD4 exome AF: 0.0480 AC: 15453 AN: 321660 Hom.: 499 Cov.: 0 AF XY: 0.0440 AC XY: 7365 AN XY: 167448

African (AFR) AF: 0.188 AC: 1428 AN: 7614

American (AMR) AF: 0.0445 AC: 432 AN: 9702

Ashkenazi Jewish (ASJ) AF: 0.0217 AC: 230 AN: 10594

East Asian (EAS) AF: 0.0416 AC: 929 AN: 22324

South Asian (SAS) AF: 0.0108 AC: 315 AN: 29114

European-Finnish (FIN) AF: 0.0752 AC: 2043 AN: 27180

Middle Eastern (MID) AF: 0.0303 AC: 46 AN: 1516

European-Non Finnish (NFE) AF: 0.0465 AC: 9043 AN: 194490

Other (OTH) AF: 0.0516 AC: 987 AN: 19126

GnomAD4 genome AF: 0.102 AC: 15585 AN: 152134 Hom.: 1222 Cov.: 31 AF XY: 0.102 AC XY: 7609 AN XY: 74394

African (AFR) AF: 0.222 AC: 9208 AN: 41434

American (AMR) AF: 0.0634 AC: 971 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0289 AC: 100 AN: 3464

East Asian (EAS) AF: 0.0343 AC: 178 AN: 5184

South Asian (SAS) AF: 0.0133 AC: 64 AN: 4830

European-Finnish (FIN) AF: 0.101 AC: 1069 AN: 10588

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0547 AC: 3723 AN: 68010

Other (OTH) AF: 0.0882 AC: 186 AN: 2108

Alfa AF: 0.0792 Hom.: 1422

Bravo AF: 0.106

Asia WGS AF: 0.0360 AC: 128 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	8.1
DANN	Benign	0.86
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs16870907; hg19: chr6-32789807;