rs3128961

Variant names:

• chr6-33082965-G-A
• rs3128961
• NM_002121.6:c.365-1985G>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.365-1985G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,088 control chromosomes in the GnomAD database, including 12,189 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 (12189 hom., cov: 32)
• Consequence: HLA-DPB1 NM_002121.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 12 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 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.365-1985G>A		intron	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.365-1985G>A		intron	N/A	ENSP00000408146.2
	HLA-DPB1	ENST00000714457.1		n.1123G>A		non_coding_transcript_exon	Exon 3 of 7
	HLA-DPB1	ENST00000714454.1		c.53-820G>A		intron	N/A	ENSP00000519716.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57075 AN: 151970 Hom.: 12167 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.376 AC: 57121 AN: 152088 Hom.: 12189 Cov.: 32 AF XY: 0.369 AC XY: 27423 AN XY: 74360

African (AFR) AF: 0.567 AC: 23520 AN: 41458

American (AMR) AF: 0.294 AC: 4497 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3470

East Asian (EAS) AF: 0.630 AC: 3259 AN: 5176

South Asian (SAS) AF: 0.338 AC: 1631 AN: 4822

European-Finnish (FIN) AF: 0.249 AC: 2632 AN: 10580

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

European-Non Finnish (NFE) AF: 0.293 AC: 19933 AN: 67966

Other (OTH) AF: 0.389 AC: 822 AN: 2112

Alfa AF: 0.332 Hom.: 3406

Bravo AF: 0.385

Asia WGS AF: 0.487 AC: 1693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.6
DANN	Benign	0.63
PhyloP100		-0.088
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: rs3128961; hg19: chr6-33050742;