rs9272346

Variant names:

• chr6-32636595-G-A
• rs9272346
• ENST00000422863.1:c.-38-826G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000422863.1(HLA-DQA1):​c.-38-826G>A variant causes a intron 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 ENST00000422863.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 166 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.621 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.-38-826G>A		intron	N/A	ENSP00000405797.1

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

African (AFR) AF: 0.477 AC: 16915 AN: 35442

American (AMR) AF: 0.633 AC: 8446 AN: 13348

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 1836 AN: 3034

East Asian (EAS) AF: 0.592 AC: 2764 AN: 4672

South Asian (SAS) AF: 0.470 AC: 1993 AN: 4240

European-Finnish (FIN) AF: 0.488 AC: 4510 AN: 9250

Middle Eastern (MID) AF: 0.655 AC: 144 AN: 220

European-Non Finnish (NFE) AF: 0.563 AC: 33524 AN: 59510

Other (OTH) AF: 0.553 AC: 1007 AN: 1822

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.5
DANN	Benign	0.40
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs9272346; hg19: chr6-32604372;