rs2856997

Positions:

• chr6-32813999-C-A
• chr6-32813999-C-G

Variant summary

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

The NM_002120.4(HLA-DOB):​c.644-166G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 620,302 control chromosomes in the GnomAD database, including 65,046 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 0.45 (15817 hom., cov: 31)
  • Exomes 𝑓: 0.45 (49229 hom.)
• Consequence: HLA-DOB NM_002120.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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 = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DOB	NM_002120.4	c.644-166G>T		intron_variant		ENST00000438763.7	NP_002111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DOB	ENST00000438763.7	c.644-166G>T		intron_variant			NM_002120.4	ENSP00000390020	P1
HLA-DOB	ENST00000648009.1	c.644-166G>T		intron_variant				ENSP00000496848	P1
HLA-DOB	ENST00000475235.1	n.1001G>T		non_coding_transcript_exon_variant	3/5
HLA-DOB	ENST00000488325.5	c.*415-166G>T		intron_variant, NMD_transcript_variant				ENSP00000436618

Frequencies

GnomAD3 genomes AF: 0.455 AC: 68990 AN: 151766 Hom.: 15800 Cov.: 31

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.452 AC: 211753 AN: 468418 Hom.: 49229 Cov.: 5 AF XY: 0.455 AC XY: 112744 AN XY: 247976

Gnomad4 AFR exome AF: 0.466

Gnomad4 AMR exome AF: 0.490

Gnomad4 ASJ exome AF: 0.452

Gnomad4 EAS exome AF: 0.528

Gnomad4 SAS exome AF: 0.541

Gnomad4 FIN exome AF: 0.529

Gnomad4 NFE exome AF: 0.420

Gnomad4 OTH exome AF: 0.437

GnomAD4 genome AF: 0.455 AC: 69045 AN: 151884 Hom.: 15817 Cov.: 31 AF XY: 0.462 AC XY: 34333 AN XY: 74262

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.453

Alfa AF: 0.427 Hom.: 26033

Bravo AF: 0.447

Asia WGS AF: 0.515 AC: 1794 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	0.14
DANN	Benign	0.41

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: rs2856997; hg19: chr6-32781776;