rs2395533

Variant names:

• chr6-32655500-C-T
• rs2395533
• XM_006715079.5:c.*826C>T

Variant summary

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

The XM_006715079.5(HLA-DQA1):​c.*826C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 145,924 control chromosomes in the GnomAD database, including 1,772 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 0.14 (1772 hom., cov: 30)
• Consequence: HLA-DQA1 XM_006715079.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

Genes affected

HLA-DQA1 (HGNC:4942): (major histocompatibility complex, class II, DQ alpha 1) HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B Lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa. It is encoded by 5 exons; exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	XM_006715079.5	c.*826C>T		downstream_gene_variant			XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.142 AC: 20664 AN: 145806 Hom.: 1768 Cov.: 30

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.142 AC: 20691 AN: 145924 Hom.: 1772 Cov.: 30 AF XY: 0.146 AC XY: 10382 AN XY: 71328

Gnomad4 AFR AF: 0.0552

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.132

Alfa AF: 0.136 Hom.: 360

Bravo AF: 0.140

Asia WGS AF: 0.152 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2395533; hg19: chr6-32623277;