6-33086565-T-C

Variant names:

• chr6-33086565-T-C
• rs1042448
• NM_002121.6:c.*31T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002121.6(HLA-DPB1):​c.*31T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000665 in 450,796 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000067 (0 hom.)
• Consequence: HLA-DPB1 NM_002121.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85
• Publications: 8 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6	c.*31T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000418931.7	NP_002112.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPB1	ENST00000418931.7	c.*31T>C		3_prime_UTR_variant	Exon 6 of 6	6	NM_002121.6	ENSP00000408146.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.00000742 AC: 1 AN: 134740 AF XY: 0.0000138

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000190

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000665 AC: 3 AN: 450796 Hom.: 0 Cov.: 0 AF XY: 0.0000122 AC XY: 3 AN XY: 245696

African (AFR) AF: 0.00 AC: 0 AN: 10824

American (AMR) AF: 0.00 AC: 0 AN: 30312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17296

East Asian (EAS) AF: 0.00 AC: 0 AN: 17616

South Asian (SAS) AF: 0.00 AC: 0 AN: 57934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3578

European-Non Finnish (NFE) AF: 0.0000119 AC: 3 AN: 251084

Other (OTH) AF: 0.00 AC: 0 AN: 23564

GnomAD4 genome Cov.: 29

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
PhyloP100		-2.8

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

Other links and lift over

dbSNP: rs1042448; hg19: chr6-33054342;