NM_002120.4:c.644-166G>T

Variant names:

• chr6-32813999-C-A
• rs2856997
• NM_002120.4:c.644-166G>T

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.644-166G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 620,302 control chromosomes in the GnomAD database, including 65,046 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 0.45 (15817 hom., cov: 31)
  • Exomes 𝑓: 0.45 (49229 hom.)
• Consequence: HLA-DOB NM_002120.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 45 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002120.4. 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
	HLA-DOB	NM_002120.4	MANE Select	c.644-166G>T		intron	N/A	NP_002111.1	P13765

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DOB	ENST00000438763.7	TSL:6 MANE Select	c.644-166G>T		intron	N/A	ENSP00000390020.2	P13765
	ENSG00000250264	ENST00000452392.2	TSL:2	c.2465-166G>T		intron	N/A	ENSP00000391806.2	E7ENX8
	HLA-DOB	ENST00000648009.1		c.644-166G>T		intron	N/A	ENSP00000496848.1	P13765

Frequencies

GnomAD3 genomes AF: 0.455 AC: 68990 AN: 151766 Hom.: 15800 Cov.: 31

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.452 AC: 211753 AN: 468418 Hom.: 49229 Cov.: 5 AF XY: 0.455 AC XY: 112744 AN XY: 247976

African (AFR) AF: 0.466 AC: 5933 AN: 12722

American (AMR) AF: 0.490 AC: 9210 AN: 18796

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 6287 AN: 13918

East Asian (EAS) AF: 0.528 AC: 16601 AN: 31426

South Asian (SAS) AF: 0.541 AC: 23910 AN: 44236

European-Finnish (FIN) AF: 0.529 AC: 16830 AN: 31786

Middle Eastern (MID) AF: 0.439 AC: 885 AN: 2016

European-Non Finnish (NFE) AF: 0.420 AC: 120383 AN: 286736

Other (OTH) AF: 0.437 AC: 11714 AN: 26782

GnomAD4 genome AF: 0.455 AC: 69045 AN: 151884 Hom.: 15817 Cov.: 31 AF XY: 0.462 AC XY: 34333 AN XY: 74262

African (AFR) AF: 0.470 AC: 19417 AN: 41354

American (AMR) AF: 0.475 AC: 7262 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1513 AN: 3466

East Asian (EAS) AF: 0.488 AC: 2523 AN: 5170

South Asian (SAS) AF: 0.555 AC: 2677 AN: 4822

European-Finnish (FIN) AF: 0.539 AC: 5691 AN: 10564

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28326 AN: 67918

Other (OTH) AF: 0.453 AC: 954 AN: 2108

Alfa AF: 0.428 Hom.: 57804

Bravo AF: 0.447

Asia WGS AF: 0.515 AC: 1794 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	0.14
DANN	Benign	0.41
PhyloP100		-1.2
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: rs2856997; hg19: chr6-32781776;