rs1042140

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002121.6(HLA-DPB1):​c.292A>C​(p.Lys98Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 31)

Consequence

HLA-DPB1
NM_002121.6 missense

Scores

18

Clinical Significance

Not reported in ClinVar

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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10368645).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HLA-DPB1NM_002121.6 linkuse as main transcriptc.292A>C p.Lys98Gln missense_variant 2/6 ENST00000418931.7 NP_002112.3 P04440I4EC15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HLA-DPB1ENST00000418931.7 linkuse as main transcriptc.292A>C p.Lys98Gln missense_variant 2/66 NM_002121.6 ENSP00000408146.2 P04440

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
55
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
0.0090
DANN
Benign
0.66
DEOGEN2
Benign
0.027
T;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.019
N
M_CAP
Benign
0.0035
T
MetaRNN
Benign
0.10
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
2.0
M;.
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-1.2
N;N
REVEL
Benign
0.28
Sift
Benign
0.054
T;T
Sift4G
Benign
0.26
T;T
Polyphen
0.083
B;.
Vest4
0.056
MutPred
0.11
Loss of methylation at K98 (P = 0.0124);.;
MVP
0.17
MPC
0.87
ClinPred
0.31
T
GERP RS
-8.0
Varity_R
0.16
gMVP
0.55

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.

Other links and lift over

dbSNP: rs1042140; hg19: chr6-33048640; API