6-32817006-C-T

Variant names:

• chr6-32817006-C-T
• rs2071469
• ENST00000452392.2:c.1933-54G>A

Variant summary

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

The ENST00000452392.2(ENSG00000250264):​c.1933-54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,333,512 control chromosomes in the GnomAD database, including 96,503 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 0.35 (10254 hom., cov: 32)
  • Exomes 𝑓: 0.37 (86249 hom.)
• Consequence: ENSG00000250264 ENST00000452392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.771

Genes affected

ENSG00000250264 (HGNC:):

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DOB	NM_002120.4	c.-55G>A		upstream_gene_variant		ENST00000438763.7	NP_002111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000250264	ENST00000452392.2	c.1933-54G>A		intron_variant	Intron 11 of 14	2		ENSP00000391806.2
HLA-DOB	ENST00000438763.7	c.-55G>A		upstream_gene_variant		6	NM_002120.4	ENSP00000390020.2

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53813 AN: 151840 Hom.: 10247 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.353

GnomAD4 exome AF: 0.374 AC: 442311 AN: 1181554 Hom.: 86249 Cov.: 15 AF XY: 0.376 AC XY: 225897 AN XY: 600544

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.471

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.491

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.492

Gnomad4 NFE exome AF: 0.356

Gnomad4 OTH exome AF: 0.363

GnomAD4 genome AF: 0.354 AC: 53842 AN: 151958 Hom.: 10254 Cov.: 32 AF XY: 0.364 AC XY: 27010 AN XY: 74258

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.358

Alfa AF: 0.355 Hom.: 9316

Bravo AF: 0.340

Asia WGS AF: 0.447 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.61

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: rs2071469; hg19: chr6-32784783; COSMIC: COSV66503396; COSMIC: COSV66503396;