rs1042140

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_002121.6(HLA-DPB1):c.292A>G(p.Lys98Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,607,872 control chromosomes in the GnomAD database, including 45,336 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.24 ( 4752 hom., cov: 31)

Exomes 𝑓: 0.23 ( 40584 hom. )

Consequence

HLA-DPB1
NM_002121.6 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: -5.80

Publications

24 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 (MetaRNN=0.0046232343).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 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	HGVSp	Effect	Exon Rank	Protein	UniProt
HLA-DPB1	NM_002121.6	MANE Select	c.292A>G	p.Lys98Glu	missense	Exon 2 of 6	NP_002112.3
HLA-DPA1	NM_001242524.2		c.-283T>C		upstream_gene	N/A	NP_001229453.1	P20036
HLA-DPA1	NM_001242525.2		c.-207T>C		upstream_gene	N/A	NP_001229454.1	X5CKE2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HLA-DPB1	ENST00000418931.7	TSL:6 MANE Select	c.292A>G	p.Lys98Glu	missense	Exon 2 of 6	ENSP00000408146.2	P04440
HLA-DPB1	ENST00000966804.1		c.292A>G	p.Lys98Glu	missense	Exon 2 of 7	ENSP00000636863.1
HLA-DPB1	ENST00000907475.1		c.292A>G	p.Lys98Glu	missense	Exon 3 of 7	ENSP00000577534.1

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36832

AN:

151860

Hom.:

4758

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.374

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.273

GnomAD2 exomes

AF:

0.246

AC:

61054

AN:

247988

AF XY:

0.254

show subpopulations

Gnomad AFR exome

AF:

0.266

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.267

Gnomad EAS exome

AF:

0.378

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.264

GnomAD4 exome

AF:

0.230

AC:

334467

AN:

1455894

Hom.:

40584

Cov.:

AF XY:

0.234

AC XY:

169307

AN XY:

724122

show subpopulations

African (AFR)

AF:

0.259

AC:

8628

AN:

33354

American (AMR)

AF:

0.188

AC:

8410

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

6960

AN:

26044

East Asian (EAS)

AF:

0.396

AC:

15697

AN:

39606

South Asian (SAS)

AF:

0.348

AC:

29862

AN:

85768

European-Finnish (FIN)

AF:

0.166

AC:

8758

AN:

52832

Middle Eastern (MID)

AF:

0.314

AC:

1804

AN:

5748

European-Non Finnish (NFE)

AF:

0.216

AC:

239777

AN:

1107750

Other (OTH)

AF:

0.242

AC:

14571

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

11276

22552

33828

45104

56380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8404

16808

25212

33616

42020

<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:

0.242

AC:

36831

AN:

151978

Hom.:

4752

Cov.:

AF XY:

0.245

AC XY:

18189

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.264

AC:

10925

AN:

41434

American (AMR)

AF:

0.231

AC:

3533

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

940

AN:

3470

East Asian (EAS)

AF:

0.374

AC:

1918

AN:

5132

South Asian (SAS)

AF:

0.358

AC:

1717

AN:

4798

European-Finnish (FIN)

AF:

0.164

AC:

1739

AN:

10590

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.224

AC:

15199

AN:

67950

Other (OTH)

AF:

0.271

AC:

572

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1427

2853

4280

5706

7133

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.230

Hom.:

1333

Bravo

AF:

0.248

TwinsUK

AF:

0.190

AC:

703

ALSPAC

AF:

0.188

AC:

726

ESP6500AA

AF:

0.249

AC:

751

ESP6500EA

AF:

0.224

AC:

1214

ExAC

AF:

0.251

AC:

30306

EpiCase

AF:

0.239

EpiControl

AF:

0.254

ClinVar

ClinVar submissions

Significance:risk factor

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Beryllium disease, chronic, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.0090

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.026

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.014

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

PhyloP100

-5.8

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.36

Sift

Benign

0.29

Sift4G

Benign

0.50

Polyphen

0.0

Vest4

0.052

MPC

1.0

ClinPred

0.010

GERP RS

-8.0

PromoterAI

0.30

Neutral

(source)

Varity_R

0.13

gMVP

0.60

Mutation Taster

=99/1

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