6-32819279-C-T

Variant names:

• chr6-32819279-C-T
• rs1894406
• ENST00000452392.2:c.1933-2327G>A

Variant summary

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

The ENST00000452392.2(ENSG00000250264):​c.1933-2327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 150,776 control chromosomes in the GnomAD database, including 9,101 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 0.34 (9101 hom., cov: 31)
• Consequence: ENSG00000250264 ENST00000452392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 38 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 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.1933-2327G>A		intron	N/A	ENSP00000391806.2	E7ENX8
	HLA-DOB	ENST00000648009.1		c.-2+1032G>A		intron	N/A	ENSP00000496848.1	P13765

Frequencies

GnomAD3 genomes AF: 0.337 AC: 50787 AN: 150656 Hom.: 9096 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.337 AC: 50814 AN: 150776 Hom.: 9101 Cov.: 31 AF XY: 0.347 AC XY: 25592 AN XY: 73770

African (AFR) AF: 0.226 AC: 9339 AN: 41322

American (AMR) AF: 0.400 AC: 6068 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1230 AN: 3432

East Asian (EAS) AF: 0.531 AC: 2747 AN: 5170

South Asian (SAS) AF: 0.444 AC: 2120 AN: 4772

European-Finnish (FIN) AF: 0.468 AC: 4934 AN: 10538

Middle Eastern (MID) AF: 0.360 AC: 103 AN: 286

European-Non Finnish (NFE) AF: 0.344 AC: 23092 AN: 67072

Other (OTH) AF: 0.347 AC: 729 AN: 2102

Alfa AF: 0.331 Hom.: 24544

Bravo AF: 0.322

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.43
DANN	Benign	0.27
PhyloP100		-2.0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1894406;

hg19: chr6-32787056;