rs3117226

Variant names:

• chr6-33089882-G-A
• rs3117226
• NM_002121.6:c.*3348G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-33089882-G-A
• chr6-33089882-G-C
• chr6-33089882-G-T

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.*3348G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,830 control chromosomes in the GnomAD database, including 9,308 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 0.33 (9308 hom., cov: 32)
• Consequence: HLA-DPB1 NM_002121.6 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881
• Publications: 24 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6	c.*3348G>A		downstream_gene_variant		ENST00000418931.7	NP_002112.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPB1	ENST00000418931.7	c.*3348G>A		downstream_gene_variant		6	NM_002121.6	ENSP00000408146.2
HLA-DPB1	ENST00000428835.6	c.*3348G>A		downstream_gene_variant		6		ENSP00000412654.2

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49611 AN: 151708 Hom.: 9286 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.327 AC: 49666 AN: 151830 Hom.: 9308 Cov.: 32 AF XY: 0.322 AC XY: 23910 AN XY: 74194

African (AFR) AF: 0.495 AC: 20447 AN: 41338

American (AMR) AF: 0.250 AC: 3825 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 518 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2824 AN: 5140

South Asian (SAS) AF: 0.250 AC: 1207 AN: 4820

European-Finnish (FIN) AF: 0.244 AC: 2576 AN: 10552

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17403 AN: 67928

Other (OTH) AF: 0.324 AC: 684 AN: 2110

Alfa AF: 0.277 Hom.: 23935

Bravo AF: 0.334

Asia WGS AF: 0.385 AC: 1336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.65
PhyloP100		-0.88

Splicing

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

Other links and lift over

dbSNP: rs3117226; hg19: chr6-33057659;