rs1042140

Positions:

• chr6-33080863-A-C
• chr6-33080863-A-G
• chr6-33080863-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.80

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 (HGNC:):

ACMG classification

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-DPB1	NM_002121.6	c.292A>C	p.Lys98Gln	missense_variant	2/6	ENST00000418931.7	NP_002112.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DPB1	ENST00000418931.7	c.292A>C	p.Lys98Gln	missense_variant	2/6	6	NM_002121.6	ENSP00000408146.2

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

Other links and lift over

dbSNP: rs1042140; hg19: chr6-33048640;