rs2071351

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002121.6(HLA-DPB1):c.100+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,571,896 control chromosomes in the GnomAD database, including 47,468 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 0.29 ( 8851 hom., cov: 32)

Exomes 𝑓: 0.21 ( 38617 hom. )

Consequence

HLA-DPB1
NM_002121.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.377

Publications

32 publications found

Variant links:

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]

HLA-DPB1 links:

HLA-DPA1 (HGNC:4938): (major histocompatibility complex, class II, DP alpha 1) HLA-DPA1 belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta (DPB) chain, 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 alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and 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]

HLA-DPA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HLA-DPB1	NM_002121.6	MANE Select	c.100+12A>G	intron	N/A	NP_002112.3
HLA-DPA1	NM_001242524.2		c.-99-2484T>C	intron	N/A	NP_001229453.1	P20036
HLA-DPA1	NM_001242525.2		c.-23-2560T>C	intron	N/A	NP_001229454.1	X5CKE2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HLA-DPB1	ENST00000418931.7	TSL:6 MANE Select	c.100+12A>G	intron	N/A	ENSP00000408146.2	P04440
HLA-DPB1	ENST00000966804.1		c.100+12A>G	intron	N/A	ENSP00000636863.1
HLA-DPA1	ENST00000419277.5	TSL:6	c.-99-2484T>C	intron	N/A	ENSP00000393566.1	P20036

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44752

AN:

152004

Hom.:

8829

Cov.:

show subpopulations

Gnomad AFR

AF:

0.514

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.687

Gnomad SAS

AF:

0.343

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.307

GnomAD2 exomes

AF:

0.244

AC:

54444

AN:

222744

AF XY:

0.243

show subpopulations

Gnomad AFR exome

AF:

0.525

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.185

Gnomad EAS exome

AF:

0.682

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.171

Gnomad OTH exome

AF:

0.208

GnomAD4 exome

AF:

0.208

AC:

294801

AN:

1419774

Hom.:

38617

Cov.:

AF XY:

0.210

AC XY:

148106

AN XY:

706940

show subpopulations

African (AFR)

AF:

0.536

AC:

17584

AN:

32794

American (AMR)

AF:

0.190

AC:

8107

AN:

42714

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

4553

AN:

25618

East Asian (EAS)

AF:

0.635

AC:

24881

AN:

39178

South Asian (SAS)

AF:

0.318

AC:

26504

AN:

83408

European-Finnish (FIN)

AF:

0.102

AC:

5267

AN:

51544

Middle Eastern (MID)

AF:

0.208

AC:

1183

AN:

5686

European-Non Finnish (NFE)

AF:

0.178

AC:

192692

AN:

1079922

Other (OTH)

AF:

0.238

AC:

14030

AN:

58910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

10537

21073

31610

42146

52683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7162

14324

21486

28648

35810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.295

AC:

44815

AN:

152122

Hom.:

8851

Cov.:

AF XY:

0.292

AC XY:

21714

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.514

AC:

21298

AN:

41456

American (AMR)

AF:

0.246

AC:

3758

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

582

AN:

3466

East Asian (EAS)

AF:

0.688

AC:

3557

AN:

5168

South Asian (SAS)

AF:

0.342

AC:

1649

AN:

4822

European-Finnish (FIN)

AF:

0.103

AC:

1088

AN:

10612

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.177

AC:

12036

AN:

67988

Other (OTH)

AF:

0.314

AC:

663

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1397

2795

4192

5590

6987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.242

Hom.:

7630

Bravo

AF:

0.314

Asia WGS

AF:

0.456

AC:

1583

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.3

(source)

DANN

Benign

0.53

PhyloP100

0.38

PromoterAI

0.0066

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over