6-32763481-G-A

Variant names:

• chr6-32763481-G-A
• rs1573649
• NM_001300790.2:c.-11C>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.-11C>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (23775 hom., cov: 32)
  • Exomes 𝑓: 0.50 (177933 hom.)
• Consequence: HLA-DQB2 NM_001300790.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714
• Publications: 42 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 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.-11C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001287719.1
	HLA-DQB2	NM_001300790.2	MANE Select	c.-11C>T		5_prime_UTR	Exon 1 of 6	NP_001287719.1
	HLA-DQB2	NM_001198858.2		c.-11C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001185787.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQB2	ENST00000437316.7	TSL:6 MANE Select	c.-11C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000396330.2
	HLA-DQB2	ENST00000437316.7	TSL:6 MANE Select	c.-11C>T		5_prime_UTR	Exon 1 of 6	ENSP00000396330.2
	HLA-DQB2	ENST00000435145.6	TSL:6	c.-11C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000410512.2

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

GnomAD2 exomes AF: 0.559 AC: 87316 AN: 156188 AF XY: 0.556

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 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

African (AFR) AF: 0.619 AC: 19584 AN: 31622

American (AMR) AF: 0.624 AC: 22338 AN: 35810

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 14370 AN: 25106

East Asian (EAS) AF: 0.668 AC: 24181 AN: 36226

South Asian (SAS) AF: 0.570 AC: 45026 AN: 78960

European-Finnish (FIN) AF: 0.529 AC: 25623 AN: 48426

Middle Eastern (MID) AF: 0.616 AC: 3499 AN: 5680

European-Non Finnish (NFE) AF: 0.481 AC: 512482 AN: 1066202

Other (OTH) AF: 0.517 AC: 29770 AN: 57592

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

African (AFR) AF: 0.619 AC: 25652 AN: 41452

American (AMR) AF: 0.587 AC: 8969 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1948 AN: 3468

East Asian (EAS) AF: 0.708 AC: 3660 AN: 5168

South Asian (SAS) AF: 0.592 AC: 2848 AN: 4814

European-Finnish (FIN) AF: 0.543 AC: 5736 AN: 10566

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.492 AC: 33392 AN: 67880

Other (OTH) AF: 0.604 AC: 1273 AN: 2108

Alfa AF: 0.512 Hom.: 98247

Bravo AF: 0.567

Asia WGS AF: 0.621 AC: 2158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.41
PhyloP100		-0.71
PromoterAI		-0.056	Neutral
Mutation Taster		=300/0	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: rs1573649; hg19: chr6-32731258; COSMIC: COSV68614827; COSMIC: COSV68614827;