rs11244

Positions:

• chr6-32812947-G-A

Variant summary

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

The NM_002120.4(HLA-DOB):​c.*269C>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 0.282 in 547,764 control chromosomes in the GnomAD database, including 22,864 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 0.27 (5777 hom., cov: 31)
  • Exomes 𝑓: 0.29 (17087 hom.)
• Consequence: HLA-DOB NM_002120.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

Genes affected

HLA-DOB (HGNC:4937): (major histocompatibility complex, class II, DO beta) HLA-DOB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DOA) and a beta chain (DOB), both anchored in the membrane. It is located in intracellular vesicles. DO suppresses peptide loading of MHC class II molecules by inhibiting HLA-DM. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DOB	NM_002120.4	c.*269C>T		3_prime_UTR_variant	6/6	ENST00000438763.7	NP_002111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DOB	ENST00000438763.7	c.*269C>T		3_prime_UTR_variant	6/6	6	NM_002120.4	ENSP00000390020.2
HLA-DOB	ENST00000648009.1	c.*269C>T		3_prime_UTR_variant	7/7			ENSP00000496848.1
HLA-DOB	ENST00000488325.5	n.*862C>T		non_coding_transcript_exon_variant	6/6	6		ENSP00000436618.1
HLA-DOB	ENST00000488325.5	n.*862C>T		3_prime_UTR_variant	6/6	6		ENSP00000436618.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41416 AN: 151898 Hom.: 5777 Cov.: 31

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.286 AC: 112996 AN: 395748 Hom.: 17087 Cov.: 0 AF XY: 0.291 AC XY: 60257 AN XY: 207388

Gnomad4 AFR exome AF: 0.278

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 0.332

Gnomad4 EAS exome AF: 0.311

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.276

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.273 AC: 41428 AN: 152016 Hom.: 5777 Cov.: 31 AF XY: 0.272 AC XY: 20183 AN XY: 74314

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.280

Alfa AF: 0.287 Hom.: 11774

Bravo AF: 0.266

Asia WGS AF: 0.272 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.69

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: rs11244; hg19: chr6-32780724;