rs9272218

Variant names:

• chr6-32634461-C-T
• rs9272218
• ENST00000422863.1:c.-39+1552C>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.-39+1552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,206 control chromosomes in the GnomAD database, including 23,260 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 0.55 (23260 hom., cov: 29)
• Consequence: HLA-DQA1 ENST00000422863.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471
• Publications: 14 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 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.-39+1552C>T		intron	N/A	ENSP00000405797.1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83369 AN: 151088 Hom.: 23239 Cov.: 29

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.552 AC: 83433 AN: 151206 Hom.: 23260 Cov.: 29 AF XY: 0.554 AC XY: 40890 AN XY: 73844

African (AFR) AF: 0.570 AC: 23435 AN: 41126

American (AMR) AF: 0.565 AC: 8582 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2024 AN: 3460

East Asian (EAS) AF: 0.464 AC: 2387 AN: 5140

South Asian (SAS) AF: 0.506 AC: 2428 AN: 4794

European-Finnish (FIN) AF: 0.616 AC: 6402 AN: 10400

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36312 AN: 67796

Other (OTH) AF: 0.587 AC: 1232 AN: 2100

Alfa AF: 0.552 Hom.: 7824

Bravo AF: 0.547

Asia WGS AF: 0.485 AC: 1687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.6
DANN	Benign	0.53
PhyloP100		-0.47

Splicing

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

Other links and lift over

dbSNP: rs9272218; hg19: chr6-32602238;