rs1042544

chr6-33086680-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.*146A>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 0.21 in 396,756 control chromosomes in the GnomAD database, including 16,843 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 0.38 (12402 hom., cov: 31)
  • Exomes 𝑓: 0.11 (4441 hom.)
• Consequence: HLA-DPB1 NM_002121.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DPB1	NM_002121.6	c.*146A>G		3_prime_UTR_variant	6/6	ENST00000418931.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DPB1	ENST00000418931.7	c.*146A>G		3_prime_UTR_variant	6/6		NM_002121.6	P1
HLA-DPB1	ENST00000416804.1	c.*133A>G		3_prime_UTR_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57572 AN: 151682 Hom.: 12380 Cov.: 31

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.105 AC: 25793 AN: 244956 Hom.: 4441 Cov.: 0 AF XY: 0.103 AC XY: 14093 AN XY: 136350

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.0360

Gnomad4 ASJ exome AF: 0.0407

Gnomad4 EAS exome AF: 0.248

Gnomad4 SAS exome AF: 0.0896

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.380 AC: 57621 AN: 151800 Hom.: 12402 Cov.: 31 AF XY: 0.373 AC XY: 27677 AN XY: 74248

Gnomad4 AFR AF: 0.568

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.392

Alfa AF: 0.324 Hom.: 3601

Bravo AF: 0.390

Asia WGS AF: 0.488 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.0
Dann	Benign	0.40

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: rs1042544; hg19: chr6-33054457; COSMIC: COSV69602312; COSMIC: COSV69602312;