rs707947

Variant names:

• chr6-32643291-A-G
• rs707947
• NM_002122.5:c.*360A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002122.5(HLA-DQA1):​c.*360A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0749 in 272,522 control chromosomes in the GnomAD database, including 3,763 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 0.15 (3138 hom., cov: 21)
  • Exomes 𝑓: 0.016 (625 hom.)
• Consequence: HLA-DQA1 NM_002122.5 3_prime_UTR
• Scores: Splicing: ADA: 0.00002682
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 11 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.*360A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5	c.613+1038A>G		intron_variant	Intron 3 of 3		XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.*360A>G		3_prime_UTR_variant	Exon 5 of 5	6	NM_002122.5	ENSP00000339398.5
HLA-DQA1	ENST00000460633.1	n.1679A>G		non_coding_transcript_exon_variant	Exon 3 of 3	6
HLA-DQA1	ENST00000395363.5	c.*21-2A>G		splice_acceptor_variant, intron_variant	Intron 4 of 4	6		ENSP00000378767.1
HLA-DQA1	ENST00000482745.5	n.*1960A>G		downstream_gene_variant		6		ENSP00000436546.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 18067 AN: 120976 Hom.: 3139 Cov.: 21

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0802

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0969

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.0155 AC: 2353 AN: 151490 Hom.: 625 Cov.: 0 AF XY: 0.0143 AC XY: 1243 AN XY: 86778

African (AFR) AF: 0.0140 AC: 59 AN: 4218

American (AMR) AF: 0.0344 AC: 241 AN: 7004

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 60 AN: 3660

East Asian (EAS) AF: 0.00809 AC: 44 AN: 5436

South Asian (SAS) AF: 0.00984 AC: 322 AN: 32724

European-Finnish (FIN) AF: 0.00608 AC: 44 AN: 7240

Middle Eastern (MID) AF: 0.0509 AC: 61 AN: 1198

European-Non Finnish (NFE) AF: 0.0169 AC: 1395 AN: 82784

Other (OTH) AF: 0.0176 AC: 127 AN: 7226

GnomAD4 genome AF: 0.149 AC: 18064 AN: 121032 Hom.: 3138 Cov.: 21 AF XY: 0.144 AC XY: 8465 AN XY: 58694

African (AFR) AF: 0.117 AC: 4113 AN: 35220

American (AMR) AF: 0.142 AC: 1517 AN: 10660

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 507 AN: 2680

East Asian (EAS) AF: 0.0812 AC: 264 AN: 3250

South Asian (SAS) AF: 0.182 AC: 738 AN: 4054

European-Finnish (FIN) AF: 0.0969 AC: 793 AN: 8180

Middle Eastern (MID) AF: 0.123 AC: 29 AN: 236

European-Non Finnish (NFE) AF: 0.177 AC: 9620 AN: 54340

Other (OTH) AF: 0.153 AC: 257 AN: 1678

Alfa AF: 0.211 Hom.: 617

Asia WGS AF: 0.190 AC: 644 AN: 3384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.28
PhyloP100		0.15
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000027
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs707947; hg19: chr6-32611068; COSMIC: COSV104421208; COSMIC: COSV104421208;