chr6-33082247-C-A

Position:

• chr6-33082247-C-A

Variant summary

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

The NM_002121.6(HLA-DPB1):​c.364+1312C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 151,618 control chromosomes in the GnomAD database, including 11,970 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 (11968 hom., cov: 31)
  • Exomes 𝑓: 0.29 (2 hom.)
• Consequence: HLA-DPB1 NM_002121.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DPB1	NM_002121.6	c.364+1312C>A		intron_variant		ENST00000418931.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DPB1	ENST00000418931.7	c.364+1312C>A		intron_variant			NM_002121.6	P1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56635 AN: 151462 Hom.: 11946 Cov.: 31

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.289 AC: 11 AN: 38 Hom.: 2 AF XY: 0.292 AC XY: 7 AN XY: 24

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.374 AC: 56680 AN: 151580 Hom.: 11968 Cov.: 31 AF XY: 0.367 AC XY: 27185 AN XY: 74052

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.389

Alfa AF: 0.275 Hom.: 2021

Bravo AF: 0.385

Asia WGS AF: 0.486 AC: 1690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.68

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: rs9277359; hg19: chr6-33050024; COSMIC: COSV69603818; COSMIC: COSV69603818;