rs9784858

Variant names:

• chr6-32819398-G-C
• rs9784858
• ENST00000452392.2:c.1933-2446C>G

Variant summary

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

The ENST00000452392.2(ENSG00000250264):​c.1933-2446C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,152 control chromosomes in the GnomAD database, including 1,267 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 0.12 (1267 hom., cov: 31)
• Consequence: ENSG00000250264 ENST00000452392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316
• Publications: 18 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000452392.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1933-2446C>G		intron	N/A	ENSP00000391806.2	E7ENX8
	HLA-DOB	ENST00000648009.1		c.-2+913C>G		intron	N/A	ENSP00000496848.1	P13765

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18073 AN: 152034 Hom.: 1259 Cov.: 31

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0795

Gnomad ASJ AF: 0.0590

Gnomad EAS AF: 0.0917

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.119 AC: 18112 AN: 152152 Hom.: 1267 Cov.: 31 AF XY: 0.119 AC XY: 8825 AN XY: 74408

African (AFR) AF: 0.202 AC: 8374 AN: 41464

American (AMR) AF: 0.0794 AC: 1215 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0590 AC: 205 AN: 3472

East Asian (EAS) AF: 0.0917 AC: 475 AN: 5178

South Asian (SAS) AF: 0.0619 AC: 299 AN: 4828

European-Finnish (FIN) AF: 0.109 AC: 1152 AN: 10600

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.0894 AC: 6079 AN: 67994

Other (OTH) AF: 0.113 AC: 239 AN: 2110

Alfa AF: 0.106 Hom.: 148

Bravo AF: 0.121

Asia WGS AF: 0.0920 AC: 321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.3
DANN	Benign	0.49
PhyloP100		0.32

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: rs9784858; hg19: chr6-32787175;