chr6-32814805-C-T

Variant names:

• chr6-32814805-C-T
• rs2071474
• NM_002120.4:c.362-204G>A

Variant summary

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

The NM_002120.4(HLA-DOB):​c.362-204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,040 control chromosomes in the GnomAD database, including 6,386 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 0.28 (6386 hom., cov: 31)
• Consequence: HLA-DOB NM_002120.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• Publications: 52 publications found

Genes affected

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]

ENSG00000250264 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DOB	NM_002120.4	c.362-204G>A		intron_variant	Intron 2 of 5	ENST00000438763.7	NP_002111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DOB	ENST00000438763.7	c.362-204G>A		intron_variant	Intron 2 of 5	6	NM_002120.4	ENSP00000390020.2
ENSG00000250264	ENST00000452392.2	c.2183-204G>A		intron_variant	Intron 13 of 14	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42127 AN: 151922 Hom.: 6378 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.277 AC: 42147 AN: 152040 Hom.: 6386 Cov.: 31 AF XY: 0.285 AC XY: 21176 AN XY: 74274

African (AFR) AF: 0.158 AC: 6562 AN: 41500

American (AMR) AF: 0.360 AC: 5499 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1154 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1836 AN: 5154

South Asian (SAS) AF: 0.402 AC: 1933 AN: 4810

European-Finnish (FIN) AF: 0.376 AC: 3966 AN: 10546

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20047 AN: 67966

Other (OTH) AF: 0.292 AC: 617 AN: 2112

Alfa AF: 0.288 Hom.: 27545

Bravo AF: 0.271

Asia WGS AF: 0.358 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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: rs2071474; hg19: chr6-32782582;