6-33082502-A-G

Variant names:

• chr6-33082502-A-G
• rs9277378
• NM_002121.6:c.364+1567A>G

Variant summary

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

The NM_002121.6(HLA-DPB1):​c.364+1567A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,746 control chromosomes in the GnomAD database, including 14,419 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 0.40 (14419 hom., cov: 31)
• Consequence: HLA-DPB1 NM_002121.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 56 publications found

Genes affected

HLA-DPB1 (HGNC:4940): (major histocompatibility complex, class II, DP beta 1) HLA-DPB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta chain (DPB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. 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. Within the DP molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002121.6. 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
	HLA-DPB1	NM_002121.6	MANE Select	c.364+1567A>G		intron	N/A	NP_002112.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DPB1	ENST00000418931.7	TSL:6 MANE Select	c.364+1567A>G		intron	N/A	ENSP00000408146.2
	HLA-DPB1	ENST00000714457.1		n.660A>G		non_coding_transcript_exon	Exon 3 of 7
	HLA-DPB1	ENST00000714454.1		c.53-1283A>G		intron	N/A	ENSP00000519716.1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60695 AN: 151626 Hom.: 14376 Cov.: 31

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.401 AC: 60780 AN: 151746 Hom.: 14419 Cov.: 31 AF XY: 0.393 AC XY: 29147 AN XY: 74154

African (AFR) AF: 0.652 AC: 26973 AN: 41344

American (AMR) AF: 0.308 AC: 4704 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3468

East Asian (EAS) AF: 0.629 AC: 3245 AN: 5160

South Asian (SAS) AF: 0.338 AC: 1621 AN: 4796

European-Finnish (FIN) AF: 0.246 AC: 2598 AN: 10548

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19905 AN: 67864

Other (OTH) AF: 0.405 AC: 852 AN: 2104

Alfa AF: 0.343 Hom.: 25840

Bravo AF: 0.415

Asia WGS AF: 0.492 AC: 1711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.9
DANN	Benign	0.52
PhyloP100		-0.15
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: rs9277378; hg19: chr6-33050279;