rs6927022

chr6-32644620-A-Gchr6-32644620-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_006715079.5(HLA-DQA1):c.613+2367A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 146,308 control chromosomes in the GnomAD database, including 14,314 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 0.42 (14314 hom., cov: 28)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA1 XM_006715079.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DQA1	XM_006715079.5	c.613+2367A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQA1	ENST00000460633.1	n.3008A>G		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.422 AC: 61666 AN: 146196 Hom.: 14310 Cov.: 28

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.413

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.422 AC: 61699 AN: 146308 Hom.: 14314 Cov.: 28 AF XY: 0.421 AC XY: 30076 AN XY: 71390

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.409

Alfa AF: 0.438 Hom.: 1822

Bravo AF: 0.454

Asia WGS AF: 0.382 AC: 1320 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.095
Dann	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6927022; hg19: chr6-32612397;