rs1049225

Positions:

• chr6-32659970-A-G
• chr6-32659970-A-T

Variant summary

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

The NM_002123.5(HLA-DQB1):​c.*266T>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 0.665 in 245,006 control chromosomes in the GnomAD database, including 58,989 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 0.76 (43903 hom., cov: 26)
  • Exomes 𝑓: 0.51 (15086 hom.)
• Consequence: HLA-DQB1 NM_002123.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285

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-AS1 (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 = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQB1	NM_002123.5	c.*266T>C		3_prime_UTR_variant	5/5	ENST00000434651.7	NP_002114.3
HLA-DQB1	NM_001243961.2	c.*266T>C		3_prime_UTR_variant	6/6		NP_001230890.1
HLA-DQB1-AS1	NR_133907.1	n.91A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQB1	ENST00000434651	c.*266T>C		3_prime_UTR_variant	5/5		NM_002123.5	ENSP00000407332.2
HLA-DQB1	ENST00000374943	c.*266T>C		3_prime_UTR_variant	6/6			ENSP00000364080.4

Frequencies

GnomAD3 genomes AF: 0.764 AC: 113781 AN: 149006 Hom.: 43875 Cov.: 26

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.799

GnomAD4 exome AF: 0.511 AC: 49028 AN: 95886 Hom.: 15086 Cov.: 0 AF XY: 0.521 AC XY: 25912 AN XY: 49690

Gnomad4 AFR exome AF: 0.432

Gnomad4 AMR exome AF: 0.554

Gnomad4 ASJ exome AF: 0.661

Gnomad4 EAS exome AF: 0.727

Gnomad4 SAS exome AF: 0.747

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.461

Gnomad4 OTH exome AF: 0.532

GnomAD4 genome AF: 0.764 AC: 113864 AN: 149120 Hom.: 43903 Cov.: 26 AF XY: 0.765 AC XY: 55662 AN XY: 72748

Gnomad4 AFR AF: 0.717

Gnomad4 AMR AF: 0.812

Gnomad4 ASJ AF: 0.852

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.885

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.756

Gnomad4 OTH AF: 0.802

Alfa AF: 0.765 Hom.: 30277

Bravo AF: 0.768

Asia WGS AF: 0.891 AC: 3101 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	0.86
DANN	Benign	0.41

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: rs1049225; hg19: chr6-32627747;