6-33085905-G-A

Variant names:

• chr6-33085905-G-A
• rs9277471
• NM_002121.6:c.757+16G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_002121.6(HLA-DPB1):​c.757+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,541,086 control chromosomes in the GnomAD database, including 84,574 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 (12451 hom., cov: 31)
  • Exomes 𝑓: 0.31 (72123 hom.)
• Consequence: HLA-DPB1 NM_002121.6 intron
• Scores: Splicing: ADA: 0.00004650
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612
• Publications: 32 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.232).
• 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.757+16G>A		intron_variant	Intron 4 of 5	ENST00000418931.7	NP_002112.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPB1	ENST00000418931.7	c.757+16G>A		intron_variant	Intron 4 of 5	6	NM_002121.6	ENSP00000408146.2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57795 AN: 151906 Hom.: 12428 Cov.: 31

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.385

GnomAD2 exomes AF: 0.321 AC: 77744 AN: 242002 AF XY: 0.317

Gnomad AFR exome AF: 0.572

Gnomad AMR exome AF: 0.219

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.633

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.290

Gnomad OTH exome AF: 0.296

GnomAD4 exome AF: 0.313 AC: 434480 AN: 1389060 Hom.: 72123 Cov.: 22 AF XY: 0.311 AC XY: 215559 AN XY: 694176

African (AFR) AF: 0.582 AC: 18582 AN: 31928

American (AMR) AF: 0.233 AC: 10218 AN: 43790

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 4848 AN: 25020

East Asian (EAS) AF: 0.597 AC: 23450 AN: 39272

South Asian (SAS) AF: 0.313 AC: 26193 AN: 83566

European-Finnish (FIN) AF: 0.257 AC: 13623 AN: 53028

Middle Eastern (MID) AF: 0.246 AC: 1378 AN: 5602

European-Non Finnish (NFE) AF: 0.302 AC: 317143 AN: 1049082

Other (OTH) AF: 0.330 AC: 19045 AN: 57772

GnomAD4 genome AF: 0.381 AC: 57846 AN: 152026 Hom.: 12451 Cov.: 31 AF XY: 0.374 AC XY: 27778 AN XY: 74324

African (AFR) AF: 0.569 AC: 23590 AN: 41426

American (AMR) AF: 0.300 AC: 4576 AN: 15274

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

East Asian (EAS) AF: 0.640 AC: 3307 AN: 5170

South Asian (SAS) AF: 0.339 AC: 1635 AN: 4820

European-Finnish (FIN) AF: 0.253 AC: 2667 AN: 10562

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

European-Non Finnish (NFE) AF: 0.300 AC: 20389 AN: 67980

Other (OTH) AF: 0.394 AC: 833 AN: 2116

Alfa AF: 0.323 Hom.: 33689

Bravo AF: 0.390

Asia WGS AF: 0.488 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	21
DANN	Benign	0.69
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000047
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.71		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.71		Position offset: 1

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

Other links and lift over

dbSNP: rs9277471; hg19: chr6-33053682; COSMIC: COSV69603197; COSMIC: COSV69603197;