6-32812947-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002120.4(HLA-DOB):​c.*269C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 396,604 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: HLA-DOB NM_002120.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000252 AC: 1 AN: 396604 Hom.: 0 Cov.: 0 AF XY: 0.00000481 AC XY: 1 AN XY: 207864

African (AFR) AF: 0.00 AC: 0 AN: 11612

American (AMR) AF: 0.00 AC: 0 AN: 16274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12530

East Asian (EAS) AF: 0.00 AC: 0 AN: 28220

South Asian (SAS) AF: 0.00 AC: 0 AN: 37472

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1796

European-Non Finnish (NFE) AF: 0.00000417 AC: 1 AN: 239696

Other (OTH) AF: 0.00 AC: 0 AN: 23488

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.70
PhyloP100		-1.2

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: rs11244; hg19: chr6-32780724;