rs2621332

Variant names:

• chr6-32812540-G-A
• rs2621332
• NM_002120.4:c.*676C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32812540-G-A
• chr6-32812540-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.*676C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,008 control chromosomes in the GnomAD database, including 34,484 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 0.67 (34484 hom., cov: 31)
• Consequence: HLA-DOB NM_002120.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 32 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DOB	NM_002120.4	c.*676C>T		downstream_gene_variant		ENST00000438763.7	NP_002111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DOB	ENST00000438763.7	c.*676C>T		downstream_gene_variant		6	NM_002120.4	ENSP00000390020.2
HLA-DOB	ENST00000648009.1	c.*676C>T		downstream_gene_variant				ENSP00000496848.1
HLA-DOB	ENST00000488325.5	n.*1269C>T		downstream_gene_variant		6		ENSP00000436618.1

Frequencies

GnomAD3 genomes AF: 0.672 AC: 101996 AN: 151890 Hom.: 34477 Cov.: 31

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.681

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.671 AC: 102040 AN: 152008 Hom.: 34484 Cov.: 31 AF XY: 0.678 AC XY: 50382 AN XY: 74298

African (AFR) AF: 0.647 AC: 26814 AN: 41418

American (AMR) AF: 0.653 AC: 9973 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2462 AN: 3472

East Asian (EAS) AF: 0.718 AC: 3712 AN: 5168

South Asian (SAS) AF: 0.804 AC: 3869 AN: 4814

European-Finnish (FIN) AF: 0.769 AC: 8133 AN: 10580

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44655 AN: 67962

Other (OTH) AF: 0.683 AC: 1444 AN: 2114

Alfa AF: 0.669 Hom.: 104336

Bravo AF: 0.657

Asia WGS AF: 0.741 AC: 2578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.61
DANN	Benign	0.54
PhyloP100		-0.15

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2621332; hg19: chr6-32780317;