rs7774954

Positions:

• chr6-32756412-C-A
• chr6-32756412-C-T

Variant summary

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

The NM_001300790.2(HLA-DQB2):​c.*41G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0706 in 1,238,654 control chromosomes in the GnomAD database, including 4,754 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 0.12 (1650 hom., cov: 31)
  • Exomes 𝑓: 0.064 (3104 hom.)
• Consequence: HLA-DQB2 NM_001300790.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQB2	NM_001300790.2	c.*41G>T		3_prime_UTR_variant	6/6	ENST00000437316.7	NP_001287719.1
HLA-DQB2	NM_001198858.2	c.*41G>T		3_prime_UTR_variant	5/5		NP_001185787.1
HLA-DQB2	XM_011514560.3	c.*41G>T		3_prime_UTR_variant	5/5		XP_011512862.1
HLA-DQB2	XM_011514561.4	c.*41G>T		3_prime_UTR_variant	4/4		XP_011512863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQB2	ENST00000437316.7	c.*41G>T		3_prime_UTR_variant	6/6		NM_001300790.2	ENSP00000396330	P1
HLA-DQB2	ENST00000411527.5	c.*41G>T		3_prime_UTR_variant	5/5			ENSP00000390431
HLA-DQB2	ENST00000427449.1	c.*41G>T		3_prime_UTR_variant	4/4			ENSP00000415997
HLA-DQB2	ENST00000435145.6	c.*822G>T		3_prime_UTR_variant	5/5			ENSP00000410512

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17688 AN: 151964 Hom.: 1648 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.00528

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0675

Gnomad OTH AF: 0.148

GnomAD3 exomes AF: 0.0595 AC: 12326 AN: 207218 Hom.: 743 AF XY: 0.0551 AC XY: 6113 AN XY: 110962

Gnomad AFR exome AF: 0.239

Gnomad AMR exome AF: 0.0807

Gnomad ASJ exome AF: 0.0741

Gnomad EAS exome AF: 0.00140

Gnomad SAS exome AF: 0.0192

Gnomad FIN exome AF: 0.00613

Gnomad NFE exome AF: 0.0594

Gnomad OTH exome AF: 0.0806

GnomAD4 exome AF: 0.0641 AC: 69694 AN: 1086572 Hom.: 3104 Cov.: 15 AF XY: 0.0615 AC XY: 34010 AN XY: 553426

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.0905

Gnomad4 ASJ exome AF: 0.0761

Gnomad4 EAS exome AF: 0.000957

Gnomad4 SAS exome AF: 0.0191

Gnomad4 FIN exome AF: 0.00770

Gnomad4 NFE exome AF: 0.0672

Gnomad4 OTH exome AF: 0.0736

GnomAD4 genome AF: 0.116 AC: 17695 AN: 152082 Hom.: 1650 Cov.: 31 AF XY: 0.112 AC XY: 8330 AN XY: 74366

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0784

Gnomad4 EAS AF: 0.00541

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.00528

Gnomad4 NFE AF: 0.0675

Gnomad4 OTH AF: 0.146

Alfa AF: 0.0756 Hom.: 578

Bravo AF: 0.137

Asia WGS AF: 0.0200 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.1
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7774954; hg19: chr6-32724189;