NM_002121.6:c.*496A>G

Variant names:

• chr6-33087030-A-G
• rs9277534
• NM_002121.6:c.*496A>G

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.*496A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 185,388 control chromosomes in the GnomAD database, including 12,483 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 (12442 hom., cov: 32)
  • Exomes 𝑓: 0.042 (41 hom.)
• Consequence: HLA-DPB1 NM_002121.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389
• Publications: 79 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 = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6	c.*496A>G		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.*496A>G		3_prime_UTR_variant	Exon 6 of 6	6	NM_002121.6	ENSP00000408146.2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57807 AN: 151952 Hom.: 12420 Cov.: 32

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.385

GnomAD4 exome AF: 0.0424 AC: 1413 AN: 33318 Hom.: 41 Cov.: 0 AF XY: 0.0424 AC XY: 723 AN XY: 17046

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.129 AC: 26 AN: 202

American (AMR) AF: 0.0250 AC: 48 AN: 1922

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 24 AN: 966

East Asian (EAS) AF: 0.125 AC: 66 AN: 530

South Asian (SAS) AF: 0.0244 AC: 92 AN: 3766

European-Finnish (FIN) AF: 0.0395 AC: 73 AN: 1850

Middle Eastern (MID) AF: 0.0179 AC: 3 AN: 168

European-Non Finnish (NFE) AF: 0.0454 AC: 1002 AN: 22092

Other (OTH) AF: 0.0434 AC: 79 AN: 1822

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.380 AC: 57856 AN: 152070 Hom.: 12442 Cov.: 32 AF XY: 0.374 AC XY: 27765 AN XY: 74326

African (AFR) AF: 0.569 AC: 23610 AN: 41466

American (AMR) AF: 0.300 AC: 4581 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3470

East Asian (EAS) AF: 0.639 AC: 3307 AN: 5176

South Asian (SAS) AF: 0.339 AC: 1633 AN: 4816

European-Finnish (FIN) AF: 0.252 AC: 2665 AN: 10574

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.300 AC: 20383 AN: 67966

Other (OTH) AF: 0.393 AC: 830 AN: 2112

Alfa AF: 0.331 Hom.: 3867

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	3.9
DANN	Benign	0.55
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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: rs9277534; hg19: chr6-33054807;