chr6-32756412-C-A

Variant names:

• chr6-32756412-C-A
• rs7774954
• NM_001300790.2:c.*41G>T

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.*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
• Publications: 22 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300790.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQB2	NM_001300790.2	MANE Select	c.*41G>T		3_prime_UTR	Exon 6 of 6	NP_001287719.1	Q5SR05
	HLA-DQB2	NM_001198858.2		c.*41G>T		3_prime_UTR	Exon 5 of 5	NP_001185787.1	P05538-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQB2	ENST00000437316.7	TSL:6 MANE Select	c.*41G>T		3_prime_UTR	Exon 6 of 6	ENSP00000396330.2	Q5SR05
	HLA-DQB2	ENST00000435145.6	TSL:6	c.*822G>T		3_prime_UTR	Exon 5 of 5	ENSP00000410512.2	A2ADX3
	HLA-DQB2	ENST00000870921.1		c.*41G>T		3_prime_UTR	Exon 5 of 5	ENSP00000540980.1

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

GnomAD2 exomes AF: 0.0595 AC: 12326 AN: 207218 AF XY: 0.0551

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 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

African (AFR) AF: 0.240 AC: 6099 AN: 25414

American (AMR) AF: 0.0905 AC: 3555 AN: 39290

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 1777 AN: 23360

East Asian (EAS) AF: 0.000957 AC: 35 AN: 36580

South Asian (SAS) AF: 0.0191 AC: 1423 AN: 74358

European-Finnish (FIN) AF: 0.00770 AC: 397 AN: 51576

Middle Eastern (MID) AF: 0.0539 AC: 268 AN: 4972

European-Non Finnish (NFE) AF: 0.0672 AC: 52612 AN: 783056

Other (OTH) AF: 0.0736 AC: 3528 AN: 47966

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

African (AFR) AF: 0.250 AC: 10338 AN: 41396

American (AMR) AF: 0.129 AC: 1977 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

East Asian (EAS) AF: 0.00541 AC: 28 AN: 5172

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4826

European-Finnish (FIN) AF: 0.00528 AC: 56 AN: 10604

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0675 AC: 4590 AN: 67998

Other (OTH) AF: 0.146 AC: 309 AN: 2116

Alfa AF: 0.0856 Hom.: 1220

Bravo AF: 0.137

Asia WGS AF: 0.0200 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.1
DANN	Benign	0.55
PhyloP100		0.063
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7774954; hg19: chr6-32724189;