rs9272346

Positions:

• chr6-32636595-G-A
• chr6-32636595-G-T

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.3568C>T 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 0.541 in 132,366 control chromosomes in the GnomAD database, including 21,794 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 0.54 (21794 hom., cov: 25)
• Consequence: HLA-DQA1-AS1 XR_007059544.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA1-AS1	XR_007059544.1	n.3568C>T		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.-38-826G>A		intron_variant				ENSP00000405797

Frequencies

GnomAD3 genomes AF: 0.541 AC: 71579 AN: 132282 Hom.: 21786 Cov.: 25

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.541 AC: 71618 AN: 132366 Hom.: 21794 Cov.: 25 AF XY: 0.536 AC XY: 34722 AN XY: 64746

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.553

Alfa AF: 0.592 Hom.: 4653

Bravo AF: 0.584

Asia WGS AF: 0.484 AC: 1676 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.5
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9272346; hg19: chr6-32604372;