6-32643157-A-G

Position:

• chr6-32643157-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002122.5(HLA-DQA1):​c.*226A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.26 (5923 hom., cov: 18)
  • Exomes 𝑓: 0.086 (5524 hom.)
• Consequence: HLA-DQA1 NM_002122.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.*226A>G		3_prime_UTR_variant	5/5	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5	c.613+904A>G		intron_variant			XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.*226A>G		3_prime_UTR_variant	5/5	6	NM_002122.5	ENSP00000339398.5

Frequencies

GnomAD3 genomes AF: 0.257 AC: 30808 AN: 119874 Hom.: 5923 Cov.: 18

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.260

GnomAD3 exomes AF: 0.0000128 AC: 1 AN: 78382 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 43596

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000647

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0863 AC: 16248 AN: 188256 Hom.: 5524 Cov.: 0 AF XY: 0.0787 AC XY: 8555 AN XY: 108734

Gnomad4 AFR exome AF: 0.0500

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.0674

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.0535

Gnomad4 FIN exome AF: 0.0436

Gnomad4 NFE exome AF: 0.0910

Gnomad4 OTH exome AF: 0.0990

GnomAD4 genome AF: 0.257 AC: 30823 AN: 119980 Hom.: 5923 Cov.: 18 AF XY: 0.250 AC XY: 14430 AN XY: 57620

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.258

Alfa AF: 0.279 Hom.: 521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	22
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.64		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.64		Position offset: 1

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

Publications

LitVar

Other links and lift over

dbSNP: rs3667; hg19: chr6-32610934;