6-33087470-T-C

Variant names:

• chr6-33087470-T-C
• rs9277542
• NM_002121.6:c.*936T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002121.6(HLA-DPB1):​c.*936T>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 0.378 in 151,402 control chromosomes in the GnomAD database, including 12,206 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 0.38 (12206 hom., cov: 31)
• Consequence: HLA-DPB1 NM_002121.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620
• Publications: 50 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: Benign. The variant received -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 = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6	c.*936T>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.*936T>C		3_prime_UTR_variant	Exon 6 of 6	6	NM_002121.6	ENSP00000408146.2
HLA-DPB1	ENST00000714457.1	n.3521T>C		non_coding_transcript_exon_variant	Exon 7 of 7
HLA-DPB1	ENST00000428835.6	c.*936T>C		3_prime_UTR_variant	Exon 6 of 6	6		ENSP00000412654.2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57195 AN: 151282 Hom.: 12184 Cov.: 31

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.378 AC: 57244 AN: 151402 Hom.: 12206 Cov.: 31 AF XY: 0.371 AC XY: 27442 AN XY: 73972

African (AFR) AF: 0.566 AC: 23231 AN: 41038

American (AMR) AF: 0.299 AC: 4559 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 643 AN: 3470

East Asian (EAS) AF: 0.638 AC: 3288 AN: 5152

South Asian (SAS) AF: 0.338 AC: 1627 AN: 4808

European-Finnish (FIN) AF: 0.246 AC: 2579 AN: 10480

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20293 AN: 67890

Other (OTH) AF: 0.391 AC: 819 AN: 2094

Alfa AF: 0.333 Hom.: 17814

Bravo AF: 0.390

Asia WGS AF: 0.487 AC: 1693 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	0.63
DANN	Benign	0.63
PhyloP100		-0.62

Splicing

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

Other links and lift over

dbSNP: rs9277542; hg19: chr6-33055247;