rs3819714

Variant names:

• chr6-32836440-G-A
• rs3819714
• NM_001290043.2:c.609-667C>T

Variant summary

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

The NM_001290043.2(TAP2):​c.609-667C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,854 control chromosomes in the GnomAD database, including 11,607 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 0.39 (11607 hom., cov: 33)
• Consequence: TAP2 NM_001290043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 23 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000250264 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.609-667C>T		intron_variant	Intron 3 of 11	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.609-667C>T		intron_variant	Intron 3 of 11		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.609-667C>T		intron_variant	Intron 3 of 11	1	NM_001290043.2	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2	c.609-667C>T		intron_variant	Intron 3 of 14	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58468 AN: 151736 Hom.: 11594 Cov.: 33

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.449

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.385 AC: 58522 AN: 151854 Hom.: 11607 Cov.: 33 AF XY: 0.381 AC XY: 28274 AN XY: 74228

African (AFR) AF: 0.455 AC: 18816 AN: 41360

American (AMR) AF: 0.466 AC: 7105 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1548 AN: 3466

East Asian (EAS) AF: 0.364 AC: 1881 AN: 5172

South Asian (SAS) AF: 0.362 AC: 1745 AN: 4816

European-Finnish (FIN) AF: 0.251 AC: 2645 AN: 10552

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23452 AN: 67926

Other (OTH) AF: 0.448 AC: 946 AN: 2112

Alfa AF: 0.363 Hom.: 27481

Bravo AF: 0.411

Asia WGS AF: 0.390 AC: 1352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.66
PhyloP100		-1.5
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: rs3819714; hg19: chr6-32804217;