rs3128968

Positions:

• chr6-33088476-T-A
• chr6-33088476-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.*1942T>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 0.252 in 151,886 control chromosomes in the GnomAD database, including 5,238 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 (5238 hom., cov: 31)
• Consequence: HLA-DPB1 NM_002121.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6	c.*1942T>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.*1942T>A		3_prime_UTR_variant	6/6		NM_002121.6	ENSP00000408146	P1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38273 AN: 151766 Hom.: 5225 Cov.: 31

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.252 AC: 38301 AN: 151886 Hom.: 5238 Cov.: 31 AF XY: 0.249 AC XY: 18497 AN XY: 74204

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.283

Alfa AF: 0.232 Hom.: 521

Bravo AF: 0.253

Asia WGS AF: 0.403 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3128968; hg19: chr6-33056253; COSMIC: COSV69603341;