ENST00000452392.2:c.1933-2153A>G

Variant names:

• chr6-32819105-T-C
• rs3763355
• ENST00000452392.2:c.1933-2153A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000452392.2(ENSG00000250264):​c.1933-2153A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 152,344 control chromosomes in the GnomAD database, including 304 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 0.054 (304 hom., cov: 33)
• Consequence: ENSG00000250264 ENST00000452392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000250264	ENST00000452392.2	c.1933-2153A>G		intron_variant	Intron 11 of 14	2		ENSP00000391806.2
HLA-DOB	ENST00000648009.1	c.-2+1206A>G		intron_variant	Intron 1 of 6			ENSP00000496848.1

Frequencies

GnomAD3 genomes AF: 0.0537 AC: 8170 AN: 152226 Hom.: 302 Cov.: 33

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0913

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0779

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0608

Gnomad OTH AF: 0.0607

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

GnomAD4 genome AF: 0.0536 AC: 8173 AN: 152344 Hom.: 304 Cov.: 33 AF XY: 0.0551 AC XY: 4100 AN XY: 74476

African (AFR) AF: 0.0132 AC: 549 AN: 41584

American (AMR) AF: 0.0917 AC: 1403 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3472

East Asian (EAS) AF: 0.0781 AC: 405 AN: 5184

South Asian (SAS) AF: 0.0717 AC: 346 AN: 4826

European-Finnish (FIN) AF: 0.0662 AC: 703 AN: 10616

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0608 AC: 4137 AN: 68034

Other (OTH) AF: 0.0591 AC: 125 AN: 2114

Alfa AF: 0.0635 Hom.: 1105

Bravo AF: 0.0539

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.85
PhyloP100		-0.39

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

Other links and lift over

dbSNP: rs3763355; hg19: chr6-32786882;