rs9272320

Variant names:

• chr6-32636347-G-A
• rs9272320
• ENST00000422863.1:c.-38-1074G>A

Variant summary

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

The ENST00000422863.1(HLA-DQA1):​c.-38-1074G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 149,828 control chromosomes in the GnomAD database, including 19,533 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 0.50 (19533 hom., cov: 28)
• Consequence: HLA-DQA1 ENST00000422863.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 12 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]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000422863.1. You can select a different transcript below to see updated ACMG assignments.

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
	HLA-DQA1	ENST00000422863.1	TSL:6	c.-38-1074G>A		intron	N/A	ENSP00000405797.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 75081 AN: 149716 Hom.: 19533 Cov.: 28

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.501 AC: 75124 AN: 149828 Hom.: 19533 Cov.: 28 AF XY: 0.494 AC XY: 36095 AN XY: 73072

African (AFR) AF: 0.407 AC: 16540 AN: 40666

American (AMR) AF: 0.567 AC: 8541 AN: 15064

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2117 AN: 3432

East Asian (EAS) AF: 0.499 AC: 2539 AN: 5088

South Asian (SAS) AF: 0.456 AC: 2160 AN: 4732

European-Finnish (FIN) AF: 0.400 AC: 4114 AN: 10282

Middle Eastern (MID) AF: 0.660 AC: 190 AN: 288

European-Non Finnish (NFE) AF: 0.554 AC: 37312 AN: 67306

Other (OTH) AF: 0.524 AC: 1091 AN: 2082

Alfa AF: 0.535 Hom.: 1733

Bravo AF: 0.517

Asia WGS AF: 0.398 AC: 1378 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.016
DANN	Benign	0.81
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs9272320; hg19: chr6-32604124;