rs1573649

chr6-32763481-G-Achr6-32763481-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001300790.2(HLA-DQB2):c.-11C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,537,556 control chromosomes in the GnomAD database, including 201,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.55 (23775 hom., cov: 32)
  • Exomes 𝑓: 0.50 (177933 hom.)
• Consequence: HLA-DQB2 NM_001300790.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714

Genes affected

HLA-DQB2 (HGNC:4945): (major histocompatibility complex, class II, DQ beta 2) HLA-DQB2 belongs to the family of HLA class II beta chain paralogs. Class II molecules are heterodimers consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. They play 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). Polymorphisms in the alpha and beta chains specify the peptide binding specificity, and typing for these polymorphisms is routinely done for bone marrow transplantation. However this gene, HLA-DQB2, is not routinely typed, as it is not thought to have an effect on transplantation. There is conflicting evidence in the literature and public sequence databases for the protein-coding capacity of HLA-DQB2. Because there is evidence of transcription and an intact ORF, HLA-DQB2 is represented in Entrez Gene and in RefSeq as a protein-coding locus. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 6-32763481-G-A is Benign according to our data. Variant chr6-32763481-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DQB2	NM_001300790.2	c.-11C>T		5_prime_UTR_variant	1/6	ENST00000437316.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQB2	ENST00000437316.7	c.-11C>T		5_prime_UTR_variant	1/6		NM_001300790.2	P1
HLA-DQB2	ENST00000411527.5	c.-11C>T		5_prime_UTR_variant	1/5
HLA-DQB2	ENST00000435145.6	c.-11C>T		5_prime_UTR_variant	1/5
HLA-DQB2	ENST00000427449.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84206 AN: 151814 Hom.: 23759 Cov.: 32

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.598

GnomAD3 exomes AF: 0.559 AC: 87316 AN: 156188 Hom.: 24963 AF XY: 0.556 AC XY: 46474 AN XY: 83534

Gnomad AFR exome AF: 0.622

Gnomad AMR exome AF: 0.622

Gnomad ASJ exome AF: 0.574

Gnomad EAS exome AF: 0.716

Gnomad SAS exome AF: 0.564

Gnomad FIN exome AF: 0.537

Gnomad NFE exome AF: 0.498

Gnomad OTH exome AF: 0.566

GnomAD4 exome AF: 0.503 AC: 696873 AN: 1385624 Hom.: 177933 Cov.: 28 AF XY: 0.505 AC XY: 345916 AN XY: 684496

Gnomad4 AFR exome AF: 0.619

Gnomad4 AMR exome AF: 0.624

Gnomad4 ASJ exome AF: 0.572

Gnomad4 EAS exome AF: 0.668

Gnomad4 SAS exome AF: 0.570

Gnomad4 FIN exome AF: 0.529

Gnomad4 NFE exome AF: 0.481

Gnomad4 OTH exome AF: 0.517

GnomAD4 genome AF: 0.555 AC: 84277 AN: 151932 Hom.: 23775 Cov.: 32 AF XY: 0.559 AC XY: 41497 AN XY: 74278

Gnomad4 AFR AF: 0.619

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.604

Alfa AF: 0.515 Hom.: 47483

Bravo AF: 0.567

Asia WGS AF: 0.621 AC: 2158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.3
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: rs1573649; hg19: chr6-32731258; COSMIC: COSV68614827; COSMIC: COSV68614827;