6-32643157-A-G

Variant names:

• chr6-32643157-A-G
• rs3667
• NM_002122.5:c.*226A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 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
• Publications: 10 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 -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• 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 rank	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.*226A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5	c.613+904A>G		intron_variant	Intron 3 of 3		XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.*226A>G		3_prime_UTR_variant	Exon 5 of 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

GnomAD2 exomes AF: 0.0000128 AC: 1 AN: 78382 AF XY: 0.00

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 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

African (AFR) AF: 0.0500 AC: 302 AN: 6042

American (AMR) AF: 0.136 AC: 1619 AN: 11898

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 430 AN: 6382

East Asian (EAS) AF: 0.154 AC: 909 AN: 5892

South Asian (SAS) AF: 0.0535 AC: 2063 AN: 38572

European-Finnish (FIN) AF: 0.0436 AC: 375 AN: 8602

Middle Eastern (MID) AF: 0.298 AC: 552 AN: 1852

European-Non Finnish (NFE) AF: 0.0910 AC: 9086 AN: 99802

Other (OTH) AF: 0.0990 AC: 912 AN: 9214

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

African (AFR) AF: 0.181 AC: 5910 AN: 32580

American (AMR) AF: 0.312 AC: 3412 AN: 10920

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 909 AN: 2874

East Asian (EAS) AF: 0.327 AC: 1291 AN: 3946

South Asian (SAS) AF: 0.233 AC: 847 AN: 3628

European-Finnish (FIN) AF: 0.192 AC: 1521 AN: 7908

Middle Eastern (MID) AF: 0.278 AC: 60 AN: 216

European-Non Finnish (NFE) AF: 0.291 AC: 16125 AN: 55488

Other (OTH) AF: 0.258 AC: 416 AN: 1612

Alfa AF: 0.274 Hom.: 537

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
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3667; hg19: chr6-32610934;