rs2395533

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

 

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
There are no transcript annotations for this variant.

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

African (AFR) AF: 0.0552 AC: 2158 AN: 39118

American (AMR) AF: 0.226 AC: 3304 AN: 14598

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 658 AN: 3332

East Asian (EAS) AF: 0.311 AC: 1575 AN: 5066

South Asian (SAS) AF: 0.141 AC: 654 AN: 4628

European-Finnish (FIN) AF: 0.174 AC: 1787 AN: 10278

Middle Eastern (MID) AF: 0.112 AC: 31 AN: 278

European-Non Finnish (NFE) AF: 0.152 AC: 9975 AN: 65716

Other (OTH) AF: 0.132 AC: 266 AN: 2012

Alfa AF: 0.136 Hom.: 1329

Bravo AF: 0.140

Asia WGS AF: 0.152 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.43
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs2395533; hg19: chr6-32623277;