rs9272535

Positions:

• chr6-32638979-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002122.5(HLA-DQA1):​c.82+1439G>A 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 0.0017 (2 hom., cov: 18)
  • Exomes 𝑓: 0.0033 (94 hom.)
• Consequence: HLA-DQA1 NM_002122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.82+1439G>A		intron_variant		ENST00000343139.11	NP_002113.2
HLA-DQA1-AS1	XR_007059544.1	n.1184C>T		non_coding_transcript_exon_variant	2/2
HLA-DQA1	XM_006715079.5	c.82+1439G>A		intron_variant			XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.82+1439G>A		intron_variant			NM_002122.5	ENSP00000339398	P1

Frequencies

GnomAD3 genomes AF: 0.00166 AC: 192 AN: 115648 Hom.: 2 Cov.: 18

Gnomad AFR AF: 0.00235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00195

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00285

Gnomad SAS AF: 0.00258

Gnomad FIN AF: 0.00360

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000847

Gnomad OTH AF: 0.00199

GnomAD3 exomes AF: 0.0000299 AC: 3 AN: 100358 Hom.: 0 AF XY: 0.0000360 AC XY: 2 AN XY: 55500

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000784

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00328 AC: 756 AN: 230626 Hom.: 94 Cov.: 0 AF XY: 0.00360 AC XY: 477 AN XY: 132640

Gnomad4 AFR exome AF: 0.00497

Gnomad4 AMR exome AF: 0.00723

Gnomad4 ASJ exome AF: 0.000732

Gnomad4 EAS exome AF: 0.00353

Gnomad4 SAS exome AF: 0.000960

Gnomad4 FIN exome AF: 0.00518

Gnomad4 NFE exome AF: 0.00328

Gnomad4 OTH exome AF: 0.00523

GnomAD4 genome AF: 0.00166 AC: 192 AN: 115760 Hom.: 2 Cov.: 18 AF XY: 0.00174 AC XY: 98 AN XY: 56346

Gnomad4 AFR AF: 0.00234

Gnomad4 AMR AF: 0.00195

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00286

Gnomad4 SAS AF: 0.00257

Gnomad4 FIN AF: 0.00360

Gnomad4 NFE AF: 0.000847

Gnomad4 OTH AF: 0.00196

Alfa AF: 0.210 Hom.: 771

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.9
DANN	Benign	0.86

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: rs9272535; hg19: chr6-32606756; COSMIC: COSV104421202; COSMIC: COSV104421202;