NM_002121.6:c.*3400G>A

Variant names:

• chr6-33089934-G-A
• rs3117225
• NM_002121.6:c.*3400G>A

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.*3400G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,054 control chromosomes in the GnomAD database, including 12,715 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 (12715 hom., cov: 32)
• Consequence: HLA-DPB1 NM_002121.6 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721
• Publications: 22 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002121.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DPB1	NM_002121.6	MANE Select	c.*3400G>A		downstream_gene	N/A	NP_002112.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DPB1	ENST00000418931.7	TSL:6 MANE Select	c.*3400G>A		downstream_gene	N/A	ENSP00000408146.2
	HLA-DPB1	ENST00000428835.6	TSL:6	c.*3400G>A		downstream_gene	N/A	ENSP00000412654.2

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58264 AN: 151936 Hom.: 12692 Cov.: 32

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.384 AC: 58316 AN: 152054 Hom.: 12715 Cov.: 32 AF XY: 0.377 AC XY: 28032 AN XY: 74350

African (AFR) AF: 0.579 AC: 24002 AN: 41444

American (AMR) AF: 0.301 AC: 4607 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 644 AN: 3472

East Asian (EAS) AF: 0.641 AC: 3317 AN: 5178

South Asian (SAS) AF: 0.340 AC: 1639 AN: 4820

European-Finnish (FIN) AF: 0.252 AC: 2664 AN: 10564

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

European-Non Finnish (NFE) AF: 0.300 AC: 20401 AN: 67982

Other (OTH) AF: 0.397 AC: 837 AN: 2110

Alfa AF: 0.338 Hom.: 23737

Bravo AF: 0.393

Asia WGS AF: 0.489 AC: 1700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.59
PhyloP100		-0.72

Splicing

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

Other links and lift over

dbSNP: rs3117225; hg19: chr6-33057711;