rs1049130

Variant names:

• chr6-32662082-A-T
• rs1049130
• NM_002123.5:c.546T>A
• HLA-DQB1 p.Asn182Lys

Your query was ambiguous. Multiple possible variants found:

• chr6-32662082-A-T
• chr6-32662082-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_002123.5(HLA-DQB1):​c.546T>A​(p.Asn182Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQB1 NM_002123.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995
• Publications: 31 publications found

Genes affected

HLA-DQB1 (HGNC:4944): (major histocompatibility complex, class II, DQ beta 1) HLA-DQB1 belongs to the HLA class II beta chain paralogs. This class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), 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 it contains six exons. Exon 1 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 DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.932

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002123.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQB1	NM_002123.5	MANE Select	c.546T>A	p.Asn182Lys	missense	Exon 3 of 5	NP_002114.3
	HLA-DQB1	NM_001243961.2		c.546T>A	p.Asn182Lys	missense	Exon 3 of 6	NP_001230890.1	Q5SU54

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQB1	ENST00000434651.7	TSL:6 MANE Select	c.546T>A	p.Asn182Lys	missense	Exon 3 of 5	ENSP00000407332.2
	HLA-DQB1	ENST00000374943.8	TSL:6	c.546T>A	p.Asn182Lys	missense	Exon 3 of 6	ENSP00000364080.4	Q5SU54
	HLA-DQB1	ENST00000399084.5	TSL:6	c.546T>A	p.Asn182Lys	missense	Exon 4 of 6	ENSP00000382034.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 125872 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1321394 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 660986

African (AFR) AF: 0.00 AC: 0 AN: 31312

American (AMR) AF: 0.00 AC: 0 AN: 37324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23856

East Asian (EAS) AF: 0.00 AC: 0 AN: 33660

South Asian (SAS) AF: 0.00 AC: 0 AN: 82322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5338

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1004528

Other (OTH) AF: 0.00 AC: 0 AN: 55138

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 125872 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 60538

African (AFR) AF: 0.00 AC: 0 AN: 35346

American (AMR) AF: 0.00 AC: 0 AN: 10854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2938

East Asian (EAS) AF: 0.00 AC: 0 AN: 3686

South Asian (SAS) AF: 0.00 AC: 0 AN: 4064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58452

Other (OTH) AF: 0.00 AC: 0 AN: 1714

Alfa AF: 0.00 Hom.: 7311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.7
DANN	Benign	0.67
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0041	T
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-1.2	T
PhyloP100		-0.99
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.016	D
gMVP		0.55
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1049130;

hg19: chr6-32629859;