rs1048381

Positions:

• chr6-32642668-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002122.5(HLA-DQA1):​c.672G>A​(p.Gly224=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 1,220,146 control chromosomes in the GnomAD database, including 4,156 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 0.0071 (4 hom., cov: 16)
  • Exomes 𝑓: 0.021 (4152 hom.)
• Consequence: HLA-DQA1 NM_002122.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.610

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-0.61 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DQA1	NM_002122.5	c.672G>A	p.Gly224=	synonymous_variant	4/5	ENST00000343139.11
HLA-DQA1	XM_006715079.5	c.613+415G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.672G>A	p.Gly224=	synonymous_variant	4/5		NM_002122.5	P1

Frequencies

GnomAD3 genomes AF: 0.00713 AC: 748 AN: 104924 Hom.: 4 Cov.: 16

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00777

Gnomad ASJ AF: 0.00125

Gnomad EAS AF: 0.00982

Gnomad SAS AF: 0.00569

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00310

Gnomad OTH AF: 0.00853

GnomAD3 exomes AF: 0.130 AC: 29319 AN: 225234 Hom.: 4110 AF XY: 0.126 AC XY: 15383 AN XY: 122494

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.237

Gnomad ASJ exome AF: 0.0531

Gnomad EAS exome AF: 0.123

Gnomad SAS exome AF: 0.122

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.0965

GnomAD4 exome AF: 0.0214 AC: 23906 AN: 1115114 Hom.: 4152 Cov.: 32 AF XY: 0.0217 AC XY: 12148 AN XY: 560146

Gnomad4 AFR exome AF: 0.0380

Gnomad4 AMR exome AF: 0.165

Gnomad4 ASJ exome AF: 0.0148

Gnomad4 EAS exome AF: 0.0406

Gnomad4 SAS exome AF: 0.0328

Gnomad4 FIN exome AF: 0.0421

Gnomad4 NFE exome AF: 0.0123

Gnomad4 OTH exome AF: 0.0200

GnomAD4 genome AF: 0.00713 AC: 749 AN: 105032 Hom.: 4 Cov.: 16 AF XY: 0.00742 AC XY: 377 AN XY: 50790

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.00788

Gnomad4 ASJ AF: 0.00125

Gnomad4 EAS AF: 0.00984

Gnomad4 SAS AF: 0.00570

Gnomad4 FIN AF: 0.0136

Gnomad4 NFE AF: 0.00310

Gnomad4 OTH AF: 0.00843

Alfa AF: 0.123 Hom.: 519

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1048381; hg19: chr6-32610445; COSMIC: COSV58239552;