rs7756516

Variant names:

• chr6-32756140-C-T
• rs7756516
• NM_001300790.2:c.*313G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001300790.2(HLA-DQB2):​c.*313G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 421,676 control chromosomes in the GnomAD database, including 58,260 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 0.50 (19803 hom., cov: 32)
  • Exomes 𝑓: 0.52 (38457 hom.)
• Consequence: HLA-DQB2 NM_001300790.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.913
• Publications: 53 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQB2	NM_001300790.2	c.*313G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000437316.7	NP_001287719.1
HLA-DQB2	NM_001198858.2	c.*313G>A		3_prime_UTR_variant	Exon 5 of 5		NP_001185787.1
HLA-DQB2	XM_011514560.3	c.*313G>A		3_prime_UTR_variant	Exon 5 of 5		XP_011512862.1
HLA-DQB2	XM_011514561.4	c.*313G>A		3_prime_UTR_variant	Exon 4 of 4		XP_011512863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQB2	ENST00000437316.7	c.*313G>A		3_prime_UTR_variant	Exon 6 of 6	6	NM_001300790.2	ENSP00000396330.2
HLA-DQB2	ENST00000435145.6	c.*1094G>A		3_prime_UTR_variant	Exon 5 of 5	6		ENSP00000410512.2
HLA-DQB2	ENST00000411527.5	c.*313G>A		3_prime_UTR_variant	Exon 5 of 5	6		ENSP00000390431.1
HLA-DQB2	ENST00000427449.1	c.*313G>A		downstream_gene_variant		6		ENSP00000415997.1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75753 AN: 151908 Hom.: 19773 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.522

GnomAD4 exome AF: 0.522 AC: 140818 AN: 269648 Hom.: 38457 Cov.: 0 AF XY: 0.527 AC XY: 72900 AN XY: 138254

African (AFR) AF: 0.383 AC: 3568 AN: 9318

American (AMR) AF: 0.580 AC: 6020 AN: 10380

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 5289 AN: 9536

East Asian (EAS) AF: 0.723 AC: 16339 AN: 22590

South Asian (SAS) AF: 0.601 AC: 7168 AN: 11928

European-Finnish (FIN) AF: 0.548 AC: 9817 AN: 17906

Middle Eastern (MID) AF: 0.637 AC: 846 AN: 1328

European-Non Finnish (NFE) AF: 0.490 AC: 83078 AN: 169564

Other (OTH) AF: 0.508 AC: 8693 AN: 17098

GnomAD4 genome AF: 0.499 AC: 75843 AN: 152028 Hom.: 19803 Cov.: 32 AF XY: 0.509 AC XY: 37827 AN XY: 74334

African (AFR) AF: 0.390 AC: 16145 AN: 41436

American (AMR) AF: 0.553 AC: 8459 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1936 AN: 3470

East Asian (EAS) AF: 0.810 AC: 4199 AN: 5186

South Asian (SAS) AF: 0.682 AC: 3285 AN: 4814

European-Finnish (FIN) AF: 0.577 AC: 6098 AN: 10562

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33791 AN: 67960

Other (OTH) AF: 0.529 AC: 1118 AN: 2114

Alfa AF: 0.490 Hom.: 54572

Bravo AF: 0.491

Asia WGS AF: 0.705 AC: 2446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.2
DANN	Benign	0.75
PhyloP100		0.91
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: rs7756516; hg19: chr6-32723917;