rs2040406

Positions:

• chr6-32635230-A-G

Variant summary

Our verdict is Benign. Variant got -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

Genes affected

HLA-DQA1-AS1 (HGNC:):

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=-0.89).
• 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/exons	MANE	Protein	UniProt
HLA-DQA1-AS1	XR_007059544.1	n.4933T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000422863.1	c.-38-2191A>G		intron_variant				ENSP00000405797

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

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.224

Alfa AF: 0.216 Hom.: 282

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2040406; hg19: chr6-32603007;