6-32634492-G-T

Variant names:

• chr6-32634492-G-T
• rs9272219
• ENST00000422863.1:c.-39+1583G>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+1583G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,384 control chromosomes in the GnomAD database, including 6,814 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 0.29 (6814 hom., cov: 30)
• Consequence: HLA-DQA1 ENST00000422863.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 114 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.317 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+1583G>T		intron	N/A	ENSP00000405797.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44013 AN: 151270 Hom.: 6813 Cov.: 30

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.291 AC: 44035 AN: 151384 Hom.: 6814 Cov.: 30 AF XY: 0.290 AC XY: 21478 AN XY: 73998

African (AFR) AF: 0.307 AC: 12634 AN: 41160

American (AMR) AF: 0.324 AC: 4937 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1026 AN: 3462

East Asian (EAS) AF: 0.252 AC: 1296 AN: 5140

South Asian (SAS) AF: 0.251 AC: 1201 AN: 4792

European-Finnish (FIN) AF: 0.274 AC: 2883 AN: 10516

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.282 AC: 19119 AN: 67806

Other (OTH) AF: 0.306 AC: 640 AN: 2092

Alfa AF: 0.294 Hom.: 23332

Bravo AF: 0.297

Asia WGS AF: 0.253 AC: 877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.21
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs9272219; hg19: chr6-32602269;