rs2854275

Positions:

• chr6-32660651-C-A

Variant summary

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

The NM_002123.5(HLA-DQB1):​c.773-402G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0963 in 146,342 control chromosomes in the GnomAD database, including 880 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 0.096 (880 hom., cov: 25)
  • Exomes 𝑓: 0.080 (1615 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQB1 NM_002123.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQB1	NM_002123.5	c.773-402G>T		intron_variant		ENST00000434651.7	NP_002114.3
HLA-DQB1	NM_001243961.2	c.796+208G>T		intron_variant			NP_001230890.1
HLA-DQB1-AS1	NR_133907.1	n.474C>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQB1	ENST00000434651.7	c.773-402G>T		intron_variant		6	NM_002123.5	ENSP00000407332.2
HLA-DQB1	ENST00000374943.8	c.796+208G>T		intron_variant		6		ENSP00000364080.4

Frequencies

GnomAD3 genomes AF: 0.0963 AC: 14081 AN: 146224 Hom.: 879 Cov.: 25

Gnomad AFR AF: 0.0688

Gnomad AMI AF: 0.0590

Gnomad AMR AF: 0.0673

Gnomad ASJ AF: 0.0583

Gnomad EAS AF: 0.0517

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0864

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0889

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0796 AC: 21885 AN: 274896 Hom.: 1615 Cov.: 2 AF XY: 0.0830 AC XY: 12145 AN XY: 146364

Gnomad4 AFR exome AF: 0.0537

Gnomad4 AMR exome AF: 0.0512

Gnomad4 ASJ exome AF: 0.0444

Gnomad4 EAS exome AF: 0.0254

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.0614

Gnomad4 NFE exome AF: 0.0853

Gnomad4 OTH exome AF: 0.0700

GnomAD4 genome AF: 0.0963 AC: 14087 AN: 146342 Hom.: 880 Cov.: 25 AF XY: 0.0939 AC XY: 6685 AN XY: 71222

Gnomad4 AFR AF: 0.0687

Gnomad4 AMR AF: 0.0671

Gnomad4 ASJ AF: 0.0583

Gnomad4 EAS AF: 0.0516

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0864

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.0879

Alfa AF: 0.112 Hom.: 813

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.76

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: rs2854275; hg19: chr6-32628428;