6-32659970-A-G

Variant names:

• chr6-32659970-A-G
• rs1049225
• NM_002123.5:c.*266T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 publications found

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:39762): (HLA-DQB1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HLA-DQB1	NM_002123.5	c.*266T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000434651.7	NP_002114.3
HLA-DQB1-AS1	NR_133907.1	n.91A>G		non_coding_transcript_exon_variant	Exon 1 of 2
HLA-DQB1	NM_001243961.2	c.*266T>C		3_prime_UTR_variant	Exon 6 of 6		NP_001230890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQB1	ENST00000434651.7	c.*266T>C		3_prime_UTR_variant	Exon 5 of 5	6	NM_002123.5	ENSP00000407332.2
HLA-DQB1	ENST00000374943.8	c.*266T>C		3_prime_UTR_variant	Exon 6 of 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

African (AFR) AF: 0.432 AC: 1547 AN: 3584

American (AMR) AF: 0.554 AC: 1400 AN: 2526

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 1885 AN: 2850

East Asian (EAS) AF: 0.727 AC: 5604 AN: 7704

South Asian (SAS) AF: 0.747 AC: 4283 AN: 5730

European-Finnish (FIN) AF: 0.447 AC: 3340 AN: 7478

Middle Eastern (MID) AF: 0.664 AC: 296 AN: 446

European-Non Finnish (NFE) AF: 0.461 AC: 27438 AN: 59484

Other (OTH) AF: 0.532 AC: 3235 AN: 6084

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

African (AFR) AF: 0.717 AC: 28917 AN: 40306

American (AMR) AF: 0.812 AC: 12178 AN: 14996

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2937 AN: 3446

East Asian (EAS) AF: 0.912 AC: 4682 AN: 5134

South Asian (SAS) AF: 0.885 AC: 4170 AN: 4710

European-Finnish (FIN) AF: 0.747 AC: 7632 AN: 10218

Middle Eastern (MID) AF: 0.887 AC: 259 AN: 292

European-Non Finnish (NFE) AF: 0.756 AC: 50679 AN: 67056

Other (OTH) AF: 0.802 AC: 1648 AN: 2056

Alfa AF: 0.764 Hom.: 70191

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
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1049225; hg19: chr6-32627747;