rs9501251

Variant names:

• chr6-33081886-A-G
• rs9501251
• NM_002121.6:c.364+951A>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.364+951A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0394 in 152,480 control chromosomes in the GnomAD database, including 168 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 0.040 (168 hom., cov: 31)
  • Exomes 𝑓: 0.0026 (0 hom.)
• Consequence: HLA-DPB1 NM_002121.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 7 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 (AFR) allele frequency at 95% confidence interval = 0.0808 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DPB1	NM_002121.6	MANE Select	c.364+951A>G		intron	N/A	NP_002112.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DPB1	ENST00000418931.7	TSL:6 MANE Select	c.364+951A>G		intron	N/A	ENSP00000408146.2
	HLA-DPB1	ENST00000966804.1		c.365-394A>G		intron	N/A	ENSP00000636863.1
	HLA-DPB1	ENST00000907475.1		c.364+951A>G		intron	N/A	ENSP00000577534.1

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 6005 AN: 151986 Hom.: 167 Cov.: 31

Gnomad AFR AF: 0.0831

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0405

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.00868

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0461

GnomAD4 exome AF: 0.00265 AC: 1 AN: 378 Hom.: 0 AF XY: 0.00403 AC XY: 1 AN XY: 248

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 90

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00400 AC: 1 AN: 250

Other (OTH) AF: 0.00 AC: 0 AN: 20

GnomAD4 genome AF: 0.0395 AC: 6011 AN: 152102 Hom.: 168 Cov.: 31 AF XY: 0.0395 AC XY: 2938 AN XY: 74360

African (AFR) AF: 0.0831 AC: 3444 AN: 41448

American (AMR) AF: 0.0404 AC: 618 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0398 AC: 138 AN: 3470

East Asian (EAS) AF: 0.0270 AC: 140 AN: 5182

South Asian (SAS) AF: 0.0239 AC: 115 AN: 4816

European-Finnish (FIN) AF: 0.00868 AC: 92 AN: 10600

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0198 AC: 1345 AN: 67992

Other (OTH) AF: 0.0456 AC: 96 AN: 2106

Alfa AF: 0.0274 Hom.: 36

Bravo AF: 0.0453

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.31
PhyloP100		0.0090
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: rs9501251; hg19: chr6-33049663;