6-32638985-T-G

Position:

• chr6-32638985-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002122.5(HLA-DQA1):​c.82+1445T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (61 hom., cov: 18)
  • Exomes 𝑓: 0.0048 (308 hom.)
• Consequence: HLA-DQA1 NM_002122.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.750

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-32638985-T-G is Benign according to our data. Variant chr6-32638985-T-G is described in ClinVar as [Benign]. Clinvar id is 2656470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.82+1445T>G		intron_variant		ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5	c.82+1445T>G		intron_variant			XP_006715142.1
HLA-DQA1-AS1	XR_007059544.1	n.1178A>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.82+1445T>G		intron_variant		6	NM_002122.5	ENSP00000339398.5

Frequencies

GnomAD3 genomes AF: 0.00201 AC: 240 AN: 119660 Hom.: 61 Cov.: 18

Gnomad AFR AF: 0.000281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00230

Gnomad ASJ AF: 0.00326

Gnomad EAS AF: 0.00182

Gnomad SAS AF: 0.0109

Gnomad FIN AF: 0.000229

Gnomad MID AF: 0.00532

Gnomad NFE AF: 0.00256

Gnomad OTH AF: 0.00453

GnomAD3 exomes AF: 0.00417 AC: 416 AN: 99792 Hom.: 112 AF XY: 0.00496 AC XY: 274 AN XY: 55208

Gnomad AFR exome AF: 0.000224

Gnomad AMR exome AF: 0.00242

Gnomad ASJ exome AF: 0.00258

Gnomad EAS exome AF: 0.00176

Gnomad SAS exome AF: 0.0119

Gnomad FIN exome AF: 0.000853

Gnomad NFE exome AF: 0.00300

Gnomad OTH exome AF: 0.00321

GnomAD4 exome AF: 0.00476 AC: 1112 AN: 233778 Hom.: 308 Cov.: 0 AF XY: 0.00559 AC XY: 752 AN XY: 134442

Gnomad4 AFR exome AF: 0.000750

Gnomad4 AMR exome AF: 0.00247

Gnomad4 ASJ exome AF: 0.00244

Gnomad4 EAS exome AF: 0.00232

Gnomad4 SAS exome AF: 0.0130

Gnomad4 FIN exome AF: 0.000685

Gnomad4 NFE exome AF: 0.00300

Gnomad4 OTH exome AF: 0.00396

GnomAD4 genome AF: 0.00200 AC: 240 AN: 119782 Hom.: 61 Cov.: 18 AF XY: 0.00224 AC XY: 131 AN XY: 58404

Gnomad4 AFR AF: 0.000280

Gnomad4 AMR AF: 0.00230

Gnomad4 ASJ AF: 0.00326

Gnomad4 EAS AF: 0.00183

Gnomad4 SAS AF: 0.0109

Gnomad4 FIN AF: 0.000229

Gnomad4 NFE AF: 0.00256

Gnomad4 OTH AF: 0.00448

Alfa AF: 0.00162 Hom.: 2

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

HLA-DQA1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.9
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs147737004; hg19: chr6-32606762;