rs241426

Positions:

• chr6-32836776-T-A
• chr6-32836776-T-G

Variant summary

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

The NM_001290043.2(TAP2):​c.608+761A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,174 control chromosomes in the GnomAD database, including 29,423 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 0.62 (29423 hom., cov: 33)
• Consequence: TAP2 NM_001290043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAP2	NM_001290043.2	c.608+761A>T		intron_variant		ENST00000374897.4
TAP2	NM_018833.3	c.608+761A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP2	ENST00000374897.4	c.608+761A>T		intron_variant		1	NM_001290043.2	A2

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93876 AN: 152056 Hom.: 29376 Cov.: 33

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.618 AC: 93981 AN: 152174 Hom.: 29423 Cov.: 33 AF XY: 0.615 AC XY: 45781 AN XY: 74396

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.598

Alfa AF: 0.473 Hom.: 1223

Bravo AF: 0.623

Asia WGS AF: 0.623 AC: 2169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.42

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: rs241426; hg19: chr6-32804553;