chr6-33087084-A-G

Position:

• chr6-33087084-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002121.6(HLA-DPB1):​c.*550A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 161,136 control chromosomes in the GnomAD database, including 5,260 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 0.25 (5239 hom., cov: 32)
  • Exomes 𝑓: 0.033 (21 hom.)
• Consequence: HLA-DPB1 NM_002121.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6	c.*550A>G		3_prime_UTR_variant	6/6	ENST00000418931.7	NP_002112.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DPB1	ENST00000418931.7	c.*550A>G		3_prime_UTR_variant	6/6		NM_002121.6	ENSP00000408146	P1
HLA-DPB1	ENST00000416804.1	c.*537A>G		3_prime_UTR_variant	5/5			ENSP00000399832

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38313 AN: 152078 Hom.: 5226 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.0329 AC: 294 AN: 8940 Hom.: 21 Cov.: 0 AF XY: 0.0345 AC XY: 154 AN XY: 4468

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.0129

Gnomad4 ASJ exome AF: 0.00952

Gnomad4 EAS exome AF: 0.260

Gnomad4 SAS exome AF: 0.00643

Gnomad4 FIN exome AF: 0.0427

Gnomad4 NFE exome AF: 0.0306

Gnomad4 OTH exome AF: 0.0377

GnomAD4 genome AF: 0.252 AC: 38341 AN: 152196 Hom.: 5239 Cov.: 32 AF XY: 0.249 AC XY: 18525 AN XY: 74392

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.282

Alfa AF: 0.250 Hom.: 6309

Bravo AF: 0.253

Asia WGS AF: 0.396 AC: 1374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs9277535; hg19: chr6-33054861;