rs3819721

Positions:

• chr6-32837021-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290043.2(TAP2):​c.608+516C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,094 control chromosomes in the GnomAD database, including 5,230 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 0.26 (5230 hom., cov: 32)
• Consequence: TAP2 NM_001290043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.608+516C>T		intron_variant		ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.608+516C>T		intron_variant			NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.608+516C>T		intron_variant		1	NM_001290043.2	ENSP00000364032	A2

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39324 AN: 151978 Hom.: 5202 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.259 AC: 39411 AN: 152094 Hom.: 5230 Cov.: 32 AF XY: 0.262 AC XY: 19486 AN XY: 74334

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.218

Alfa AF: 0.248 Hom.: 8947

Bravo AF: 0.252

Asia WGS AF: 0.299 AC: 1043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.89

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: rs3819721; hg19: chr6-32804798;