rs1042448

Positions:

• chr6-33086565-T-A
• chr6-33086565-T-C

Variant summary

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

The NM_002121.6(HLA-DPB1):​c.*31T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 531,006 control chromosomes in the GnomAD database, including 24,847 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 0.37 (12062 hom., cov: 29)
  • Exomes 𝑓: 0.15 (12785 hom.)
• Consequence: HLA-DPB1 NM_002121.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85

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 = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6	c.*31T>A		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.*31T>A		3_prime_UTR_variant	6/6	6	NM_002121.6	ENSP00000408146.2
HLA-DPB1	ENST00000416804.1	c.*18T>A		3_prime_UTR_variant	5/5	6		ENSP00000399832.2

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56341 AN: 150430 Hom.: 12040 Cov.: 29

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.375

GnomAD3 exomes AF: 0.00615 AC: 828 AN: 134740 Hom.: 217 AF XY: 0.00536 AC XY: 387 AN XY: 72256

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.000131

Gnomad ASJ exome AF: 0.000862

Gnomad EAS exome AF: 0.00876

Gnomad SAS exome AF: 0.0000996

Gnomad FIN exome AF: 0.0136

Gnomad NFE exome AF: 0.00900

Gnomad OTH exome AF: 0.00227

GnomAD4 exome AF: 0.146 AC: 55722 AN: 380460 Hom.: 12785 Cov.: 0 AF XY: 0.140 AC XY: 28915 AN XY: 206336

Gnomad4 AFR exome AF: 0.355

Gnomad4 AMR exome AF: 0.0598

Gnomad4 ASJ exome AF: 0.0635

Gnomad4 EAS exome AF: 0.437

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.375 AC: 56390 AN: 150546 Hom.: 12062 Cov.: 29 AF XY: 0.367 AC XY: 27018 AN XY: 73578

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.383

Alfa AF: 0.238 Hom.: 1070

Bravo AF: 0.389

Asia WGS AF: 0.480 AC: 1665 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	2.3
DANN	Benign	0.59

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: rs1042448; hg19: chr6-33054342; COSMIC: COSV69602356; COSMIC: COSV69602356;