rs9272723

chr6-32641650-T-C

Variant summary

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

The NM_002122.5(HLA-DQA1):c.331+92T>C variant causes a intron 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 0.085 (716 hom., cov: 13)
  • Exomes 𝑓: 0.033 (6755 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA1 NM_002122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987

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 (NFE) allele frequency at 95% confidence interval = 0.0965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DQA1	NM_002122.5	c.331+92T>C		intron_variant		ENST00000343139.11
HLA-DQA1	XM_006715079.5	c.331+92T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.331+92T>C		intron_variant			NM_002122.5	P1

Frequencies

GnomAD3 genomes AF: 0.0849 AC: 5855 AN: 68982 Hom.: 716 Cov.: 13

Gnomad AFR AF: 0.0706

Gnomad AMI AF: 0.0798

Gnomad AMR AF: 0.0837

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0662

Gnomad SAS AF: 0.0752

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.368

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.0873

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0326 AC: 16399 AN: 503252 Hom.: 6755 AF XY: 0.0336 AC XY: 8894 AN XY: 264696

Gnomad4 AFR exome AF: 0.0320

Gnomad4 AMR exome AF: 0.0641

Gnomad4 ASJ exome AF: 0.0466

Gnomad4 EAS exome AF: 0.0200

Gnomad4 SAS exome AF: 0.0411

Gnomad4 FIN exome AF: 0.0129

Gnomad4 NFE exome AF: 0.0314

Gnomad4 OTH exome AF: 0.0359

GnomAD4 genome AF: 0.0848 AC: 5859 AN: 69052 Hom.: 716 Cov.: 13 AF XY: 0.0820 AC XY: 2754 AN XY: 33590

Gnomad4 AFR AF: 0.0705

Gnomad4 AMR AF: 0.0838

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.0665

Gnomad4 SAS AF: 0.0752

Gnomad4 FIN AF: 0.0477

Gnomad4 NFE AF: 0.0994

Gnomad4 OTH AF: 0.0872

Alfa AF: 0.549 Hom.: 4243

Asia WGS AF: 0.480 AC: 1656 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.0
Dann	Benign	0.44

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: rs9272723; hg19: chr6-32609427; COSMIC: COSV58239693; COSMIC: COSV58239693;