rs11244

Variant names:

• chr6-32812947-G-A
• rs11244
• NM_002120.4:c.*269C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32812947-G-A
• chr6-32812947-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 54 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HLA-DOB	NM_002120.4	c.*269C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000438763.7	NP_002111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DOB	ENST00000438763.7	c.*269C>T		3_prime_UTR_variant	Exon 6 of 6	6	NM_002120.4	ENSP00000390020.2

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

African (AFR) AF: 0.278 AC: 3224 AN: 11596

American (AMR) AF: 0.202 AC: 3277 AN: 16252

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 4149 AN: 12490

East Asian (EAS) AF: 0.311 AC: 8746 AN: 28150

South Asian (SAS) AF: 0.325 AC: 12155 AN: 37376

European-Finnish (FIN) AF: 0.276 AC: 7032 AN: 25454

Middle Eastern (MID) AF: 0.365 AC: 654 AN: 1792

European-Non Finnish (NFE) AF: 0.281 AC: 67219 AN: 239190

Other (OTH) AF: 0.279 AC: 6540 AN: 23448

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

African (AFR) AF: 0.281 AC: 11653 AN: 41448

American (AMR) AF: 0.216 AC: 3297 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1129 AN: 3466

East Asian (EAS) AF: 0.248 AC: 1283 AN: 5164

South Asian (SAS) AF: 0.301 AC: 1452 AN: 4822

European-Finnish (FIN) AF: 0.276 AC: 2916 AN: 10556

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18797 AN: 67972

Other (OTH) AF: 0.280 AC: 591 AN: 2108

Alfa AF: 0.288 Hom.: 26966

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
PhyloP100		-1.2
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: rs11244; hg19: chr6-32780724;