rs2040406

Variant names:

• chr6-32635230-A-G
• rs2040406
• XR_007059544.1:n.4933T>C

Variant summary

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

The XR_007059544.1(HLA-DQA1-AS1):​n.4933T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,116 control chromosomes in the GnomAD database, including 4,142 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 0.22 (4142 hom., cov: 32)
• Consequence: HLA-DQA1-AS1 XR_007059544.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 44 publications found

Genes affected

HLA-DQA1-AS1 (HGNC:56667): (HLA-DQA1 antisense RNA 1)

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1-AS1	XR_007059544.1	n.4933T>C		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000422863.1	c.-38-2191A>G		intron_variant	Intron 3 of 3	6		ENSP00000405797.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33985 AN: 151998 Hom.: 4141 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.224 AC: 34010 AN: 152116 Hom.: 4142 Cov.: 32 AF XY: 0.225 AC XY: 16707 AN XY: 74364

African (AFR) AF: 0.288 AC: 11958 AN: 41494

American (AMR) AF: 0.256 AC: 3915 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1012 AN: 5174

South Asian (SAS) AF: 0.175 AC: 844 AN: 4824

European-Finnish (FIN) AF: 0.237 AC: 2509 AN: 10568

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12770 AN: 67978

Other (OTH) AF: 0.224 AC: 473 AN: 2110

Alfa AF: 0.345 Hom.: 1723

Bravo AF: 0.229

Asia WGS AF: 0.178 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.38
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs2040406; hg19: chr6-32603007;