6-32839009-T-G

Variant names:

• chr6-32839009-T-G
• rs4713598
• ENST00000452392.2:c.-361A>C

Variant summary

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

The ENST00000452392.2(ENSG00000250264):​c.-361A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,148 control chromosomes in the GnomAD database, including 12,713 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 0.40 (12713 hom., cov: 33)
• Consequence: ENSG00000250264 ENST00000452392.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.673
• Publications: 37 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000452392.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000250264	ENST00000452392.2	TSL:2	c.-361A>C		upstream_gene	N/A	ENSP00000391806.2
	TAP2	ENST00000861086.1		c.-361A>C		upstream_gene	N/A	ENSP00000531145.1
	TAP2	ENST00000861088.1		c.-361A>C		upstream_gene	N/A	ENSP00000531147.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61597 AN: 152030 Hom.: 12712 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.405 AC: 61606 AN: 152148 Hom.: 12713 Cov.: 33 AF XY: 0.402 AC XY: 29906 AN XY: 74388

African (AFR) AF: 0.367 AC: 15260 AN: 41526

American (AMR) AF: 0.412 AC: 6295 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1331 AN: 3472

East Asian (EAS) AF: 0.412 AC: 2134 AN: 5174

South Asian (SAS) AF: 0.467 AC: 2252 AN: 4818

European-Finnish (FIN) AF: 0.358 AC: 3789 AN: 10580

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29136 AN: 67970

Other (OTH) AF: 0.408 AC: 860 AN: 2110

Alfa AF: 0.431 Hom.: 37996

Bravo AF: 0.405

Asia WGS AF: 0.402 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.8
DANN	Benign	0.75
PhyloP100		0.67
PromoterAI		-0.012	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4713598; hg19: chr6-32806786;