6-32659875-C-G

Position:

• chr6-32659875-C-G

Variant summary

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

The NM_002123.5(HLA-DQB1):​c.*361G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 150,970 control chromosomes in the GnomAD database, including 10,790 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 0.37 (10790 hom., cov: 28)
  • Exomes 𝑓: 0.076 (46 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQB1 NM_002123.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.78

Genes affected

HLA-DQB1 (HGNC:4944): (major histocompatibility complex, class II, DQ beta 1) HLA-DQB1 belongs to the HLA class II beta chain paralogs. This 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 beta chain is approximately 26-28 kDa and it contains six exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

HLA-DQB1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQB1	NM_002123.5	c.*361G>C		3_prime_UTR_variant	5/5	ENST00000434651.7	NP_002114.3
HLA-DQB1	NM_001243961.2	c.*361G>C		3_prime_UTR_variant	6/6		NP_001230890.1
HLA-DQB1-AS1	NR_133907.1	n.-5C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQB1	ENST00000434651	c.*361G>C		3_prime_UTR_variant	5/5		NM_002123.5	ENSP00000407332.2
HLA-DQB1	ENST00000374943	c.*361G>C		3_prime_UTR_variant	6/6			ENSP00000364080.4

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55679 AN: 150852 Hom.: 10779 Cov.: 28

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.374

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0764 AC: 1098 AN: 14376 Hom.: 46 Cov.: 0 AF XY: 0.0769 AC XY: 565 AN XY: 7348

Gnomad4 AFR exome AF: 0.0371

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.0925

Gnomad4 SAS exome AF: 0.0404

Gnomad4 FIN exome AF: 0.0493

Gnomad4 NFE exome AF: 0.0814

Gnomad4 OTH exome AF: 0.0601

GnomAD4 genome AF: 0.369 AC: 55728 AN: 150970 Hom.: 10790 Cov.: 28 AF XY: 0.372 AC XY: 27390 AN XY: 73694

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.373

Alfa AF: 0.368 Hom.: 1296

Bravo AF: 0.381

Asia WGS AF: 0.371 AC: 1291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.099
DANN	Benign	0.16

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: rs4993986; hg19: chr6-32627652;