6-32819793-T-C

Variant names:

• chr6-32819793-T-C
• rs2857106
• ENST00000452392.2:c.1933-2841A>G

Variant summary

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

The ENST00000452392.2(ENSG00000250264):​c.1933-2841A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,152 control chromosomes in the GnomAD database, including 3,063 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 0.19 (3063 hom., cov: 31)
• Consequence: ENSG00000250264 ENST00000452392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 42 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 = 0.263 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.1933-2841A>G		intron_variant	Intron 11 of 14	2		ENSP00000391806.2
HLA-DOB	ENST00000648009.1	c.-2+518A>G		intron_variant	Intron 1 of 6			ENSP00000496848.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29485 AN: 152034 Hom.: 3060 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.194 AC: 29509 AN: 152152 Hom.: 3063 Cov.: 31 AF XY: 0.199 AC XY: 14829 AN XY: 74390

African (AFR) AF: 0.146 AC: 6044 AN: 41530

American (AMR) AF: 0.270 AC: 4129 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 768 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1254 AN: 5182

South Asian (SAS) AF: 0.242 AC: 1167 AN: 4816

European-Finnish (FIN) AF: 0.256 AC: 2708 AN: 10574

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12688 AN: 67976

Other (OTH) AF: 0.199 AC: 419 AN: 2110

Alfa AF: 0.188 Hom.: 9887

Bravo AF: 0.196

Asia WGS AF: 0.244 AC: 845 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	3.5
DANN	Benign	0.79
PhyloP100		-0.11

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: rs2857106; hg19: chr6-32787570;