rs1048087

Variant names:

• chr6-32641509-C-T
• rs1048087
• NM_002122.5:c.282C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002122.5(HLA-DQA1):​c.282C>T​(p.His94His) variant causes a synonymous 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00076 (3 hom., cov: 13)
  • Exomes 𝑓: 0.0014 (513 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA1 NM_002122.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.11
• Publications: 19 publications found

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:56667): (HLA-DQA1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.004).
• BP6: Variant 6-32641509-C-T is Benign according to our data. Variant chr6-32641509-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3910526.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.11 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.282C>T	p.His94His	synonymous_variant	Exon 2 of 5	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5	c.282C>T	p.His94His	synonymous_variant	Exon 2 of 4		XP_006715142.1
HLA-DQA1-AS1	XR_007059544.1	n.-199G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.282C>T	p.His94His	synonymous_variant	Exon 2 of 5	6	NM_002122.5	ENSP00000339398.5

Frequencies

GnomAD3 genomes AF: 0.000776 AC: 68 AN: 87574 Hom.: 3 Cov.: 13

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000566

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00148

Gnomad SAS AF: 0.000361

Gnomad FIN AF: 0.000910

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00102

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00513 AC: 795 AN: 155042 AF XY: 0.00348

Gnomad AFR exome AF: 0.00593

Gnomad AMR exome AF: 0.00499

Gnomad ASJ exome AF: 0.00612

Gnomad EAS exome AF: 0.00406

Gnomad FIN exome AF: 0.00199

Gnomad NFE exome AF: 0.00700

Gnomad OTH exome AF: 0.00358

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00144 AC: 1332 AN: 925486 Hom.: 513 Cov.: 23 AF XY: 0.00170 AC XY: 790 AN XY: 463978

African (AFR) AF: 0.00144 AC: 35 AN: 24224

American (AMR) AF: 0.00747 AC: 144 AN: 19288

Ashkenazi Jewish (ASJ) AF: 0.00310 AC: 48 AN: 15480

East Asian (EAS) AF: 0.00174 AC: 46 AN: 26422

South Asian (SAS) AF: 0.00247 AC: 153 AN: 61980

European-Finnish (FIN) AF: 0.00133 AC: 52 AN: 39054

Middle Eastern (MID) AF: 0.000607 AC: 2 AN: 3294

European-Non Finnish (NFE) AF: 0.00115 AC: 800 AN: 696566

Other (OTH) AF: 0.00133 AC: 52 AN: 39178

GnomAD4 genome AF: 0.000764 AC: 67 AN: 87666 Hom.: 3 Cov.: 13 AF XY: 0.000798 AC XY: 34 AN XY: 42628

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000505 AC: 13 AN: 25726

American (AMR) AF: 0.000425 AC: 3 AN: 7062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1814

East Asian (EAS) AF: 0.00148 AC: 4 AN: 2696

South Asian (SAS) AF: 0.000360 AC: 1 AN: 2776

European-Finnish (FIN) AF: 0.000910 AC: 6 AN: 6596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 122

European-Non Finnish (NFE) AF: 0.00102 AC: 40 AN: 39188

Other (OTH) AF: 0.00 AC: 0 AN: 1160

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.507 Hom.: 6497

Asia WGS AF: 0.349 AC: 1189 AN: 3402

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.50
DANN	Benign	0.57
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1048087; hg19: chr6-32609286; COSMIC: COSV58238158; COSMIC: COSV58238158;