rs1894408

chr6-32819056-C-Gchr6-32819056-C-T

Variant summary

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

The ENST00000648009.1(HLA-DOB):c.-2+1255G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,064 control chromosomes in the GnomAD database, including 12,839 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 0.41 (12839 hom., cov: 32)
• Consequence: HLA-DOB ENST00000648009.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602

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 (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DOB	ENST00000648009.1	c.-2+1255G>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62026 AN: 151946 Hom.: 12824 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.408 AC: 62080 AN: 152064 Hom.: 12839 Cov.: 32 AF XY: 0.418 AC XY: 31030 AN XY: 74318

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.413

Alfa AF: 0.386 Hom.: 1691

Bravo AF: 0.402

Asia WGS AF: 0.469 AC: 1631 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	1.6
Dann	Benign	0.73

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: rs1894408; hg19: chr6-32786833;