rs1894408

Variant names:

• chr6-32819056-C-G
• rs1894408
• ENST00000452392.2:c.1933-2104G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-32819056-C-G
• chr6-32819056-C-T

Variant summary

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

The ENST00000452392.2(ENSG00000250264):​c.1933-2104G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,064 control chromosomes in the GnomAD database, including 12,839 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 0.41 (12839 hom., cov: 32)
• Consequence: ENSG00000250264 ENST00000452392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• Publications: 28 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1933-2104G>C		intron	N/A	ENSP00000391806.2
	HLA-DOB	ENST00000648009.1		c.-2+1255G>C		intron	N/A	ENSP00000496848.1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62026 AN: 151946 Hom.: 12824 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.408 AC: 62080 AN: 152064 Hom.: 12839 Cov.: 32 AF XY: 0.418 AC XY: 31030 AN XY: 74318

African (AFR) AF: 0.396 AC: 16398 AN: 41448

American (AMR) AF: 0.447 AC: 6831 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1327 AN: 3466

East Asian (EAS) AF: 0.568 AC: 2940 AN: 5180

South Asian (SAS) AF: 0.453 AC: 2187 AN: 4826

European-Finnish (FIN) AF: 0.515 AC: 5437 AN: 10552

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25517 AN: 67992

Other (OTH) AF: 0.413 AC: 870 AN: 2106

Alfa AF: 0.386 Hom.: 1691

Bravo AF: 0.402

Asia WGS AF: 0.469 AC: 1631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.73
PhyloP100		-0.60

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: rs1894408; hg19: chr6-32786833;