6-33086165-T-C

Position:

• chr6-33086165-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.758-54T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,338,954 control chromosomes in the GnomAD database, including 31,333 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 (5241 hom., cov: 31)
  • Exomes 𝑓: 0.18 (26092 hom.)
• Consequence: HLA-DPB1 NM_002121.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6	c.758-54T>C		intron_variant		ENST00000418931.7	NP_002112.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DPB1	ENST00000418931.7	c.758-54T>C		intron_variant		6	NM_002121.6	ENSP00000408146.2
HLA-DPB1	ENST00000416804.1	c.673-54T>C		intron_variant		6		ENSP00000399832.2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38273 AN: 151826 Hom.: 5228 Cov.: 31

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.182 AC: 216590 AN: 1187008 Hom.: 26092 AF XY: 0.188 AC XY: 113011 AN XY: 602180

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.252 AC: 38301 AN: 151946 Hom.: 5241 Cov.: 31 AF XY: 0.249 AC XY: 18509 AN XY: 74274

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.282

Alfa AF: 0.256 Hom.: 4086

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	-0.88
CADD	Benign	9.3
DANN	Benign	0.50

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: rs9277489; hg19: chr6-33053942; COSMIC: COSV69602692; COSMIC: COSV69602692;