NM_002123.5:c.546T>C

Variant names:

• chr6-32662082-A-G
• rs1049130
• NM_002123.5:c.546T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002123.5(HLA-DQB1):​c.546T>C​(p.Asn182Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,325,790 control chromosomes in the GnomAD database, including 209,468 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (17754 hom., cov: 20)
  • Exomes 𝑓: 0.50 (191714 hom.)
• Consequence: HLA-DQB1 NM_002123.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995
• Publications: 30 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.995 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

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>C	p.Asn182Asn	synonymous	Exon 3 of 5	NP_002114.3
	HLA-DQB1	NM_001243961.2		c.546T>C	p.Asn182Asn	synonymous	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>C	p.Asn182Asn	synonymous	Exon 3 of 5	ENSP00000407332.2
	HLA-DQB1	ENST00000374943.8	TSL:6	c.546T>C	p.Asn182Asn	synonymous	Exon 3 of 6	ENSP00000364080.4	Q5SU54
	HLA-DQB1	ENST00000399084.5	TSL:6	c.546T>C	p.Asn182Asn	synonymous	Exon 4 of 6	ENSP00000382034.1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 59810 AN: 120348 Hom.: 17732 Cov.: 20

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.522

GnomAD2 exomes AF: 0.617 AC: 148641 AN: 240820 AF XY: 0.612

Gnomad AFR exome AF: 0.495

Gnomad AMR exome AF: 0.770

Gnomad ASJ exome AF: 0.689

Gnomad EAS exome AF: 0.815

Gnomad FIN exome AF: 0.616

Gnomad NFE exome AF: 0.545

Gnomad OTH exome AF: 0.596

GnomAD4 exome AF: 0.500 AC: 602651 AN: 1205366 Hom.: 191714 Cov.: 37 AF XY: 0.505 AC XY: 305773 AN XY: 604990

African (AFR) AF: 0.458 AC: 13279 AN: 28978

American (AMR) AF: 0.697 AC: 23845 AN: 34220

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 14507 AN: 22324

East Asian (EAS) AF: 0.798 AC: 25595 AN: 32066

South Asian (SAS) AF: 0.614 AC: 48641 AN: 79164

European-Finnish (FIN) AF: 0.541 AC: 23734 AN: 43876

Middle Eastern (MID) AF: 0.580 AC: 2876 AN: 4958

European-Non Finnish (NFE) AF: 0.466 AC: 423510 AN: 908794

Other (OTH) AF: 0.523 AC: 26664 AN: 50986

GnomAD4 genome AF: 0.497 AC: 59858 AN: 120424 Hom.: 17754 Cov.: 20 AF XY: 0.501 AC XY: 29021 AN XY: 57920

African (AFR) AF: 0.449 AC: 15324 AN: 34092

American (AMR) AF: 0.552 AC: 5675 AN: 10290

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 1819 AN: 2828

East Asian (EAS) AF: 0.776 AC: 2784 AN: 3586

South Asian (SAS) AF: 0.624 AC: 2481 AN: 3974

European-Finnish (FIN) AF: 0.529 AC: 3942 AN: 7454

Middle Eastern (MID) AF: 0.640 AC: 155 AN: 242

European-Non Finnish (NFE) AF: 0.474 AC: 26369 AN: 55624

Other (OTH) AF: 0.529 AC: 889 AN: 1680

Alfa AF: 0.545 Hom.: 7311

Asia WGS AF: 0.775 AC: 2699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.081
DANN	Benign	0.34
PhyloP100		-0.99
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1049130; hg19: chr6-32629859; COSMIC: COSV66573493; COSMIC: COSV66573493;