Variant 6-33080863-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K98R) has been classified as Likely benign.

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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DPB1	NM_002121.6 linkuse as main transcript	c.292A>G	p.Lys98Glu	missense_variant	2/6	ENST00000418931.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DPB1	ENST00000418931.7 linkuse as main transcript	c.292A>G	p.Lys98Glu	missense_variant	2/6		NM_002121.6	P1

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

GnomAD3 exomes

AF:

0.246

AC:

61054

AN:

247988

Hom.:

8236

AF XY:

0.254

AC XY:

34068

AN XY:

134314

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 SAS exome

AF:

0.349

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

Gnomad4 AFR exome

AF:

0.259

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.267

Gnomad4 EAS exome

AF:

0.396

Gnomad4 SAS exome

AF:

0.348

Gnomad4 FIN exome

AF:

0.166

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.242

GnomAD4 genome

AF:

0.242

AC:

36831

AN:

151978

Hom.:

4752

Cov.:

AF XY:

0.245

AC XY:

18189

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.264

Gnomad4 AMR

AF:

0.231

Gnomad4 ASJ

AF:

0.271

Gnomad4 EAS

AF:

0.374

Gnomad4 SAS

AF:

0.358

Gnomad4 FIN

AF:

0.164

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.271

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

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Beryllium disease, chronic, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Nov 07, 2000

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.0090

DANN

Benign

0.42

DEOGEN2

Benign

0.026

T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.014

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.4

N;N

REVEL

Uncertain

0.36

Sift

Benign

0.29

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.0

B;.

Vest4

0.052

MPC

1.0

ClinPred

0.010

GERP RS

-8.0

Varity_R

0.13

gMVP

0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over