rs41544112

Variant names:

• chr6-32662143-C-T
• rs41544112
• NM_002123.5:c.485G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002123.5(HLA-DQB1):​c.485G>A​(p.Arg162Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0467 in 1,455,450 control chromosomes in the GnomAD database, including 7,618 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.056 (506 hom., cov: 18)
  • Exomes 𝑓: 0.046 (7112 hom.)
• Consequence: HLA-DQB1 NM_002123.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004396856).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQB1	NM_002123.5	c.485G>A	p.Arg162Gln	missense_variant	Exon 3 of 5	ENST00000434651.7	NP_002114.3
HLA-DQB1	NM_001243961.2	c.485G>A	p.Arg162Gln	missense_variant	Exon 3 of 6		NP_001230890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQB1	ENST00000434651.7	c.485G>A	p.Arg162Gln	missense_variant	Exon 3 of 5	6	NM_002123.5	ENSP00000407332.2
HLA-DQB1	ENST00000374943.8	c.485G>A	p.Arg162Gln	missense_variant	Exon 3 of 6	6		ENSP00000364080.4

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 6777 AN: 121520 Hom.: 505 Cov.: 18

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.0503

Gnomad AMR AF: 0.0500

Gnomad ASJ AF: 0.0581

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.0289

Gnomad FIN AF: 0.0436

Gnomad MID AF: 0.0240

Gnomad NFE AF: 0.0528

Gnomad OTH AF: 0.0578

GnomAD3 exomes AF: 0.0409 AC: 10011 AN: 244568 Hom.: 358 AF XY: 0.0411 AC XY: 5466 AN XY: 133110

Gnomad AFR exome AF: 0.0603

Gnomad AMR exome AF: 0.0254

Gnomad ASJ exome AF: 0.0498

Gnomad EAS exome AF: 0.0405

Gnomad SAS exome AF: 0.0240

Gnomad FIN exome AF: 0.0352

Gnomad NFE exome AF: 0.0477

Gnomad OTH exome AF: 0.0473

GnomAD4 exome AF: 0.0459 AC: 61243 AN: 1333826 Hom.: 7112 Cov.: 36 AF XY: 0.0451 AC XY: 30111 AN XY: 668254

Gnomad4 AFR exome AF: 0.0614

Gnomad4 AMR exome AF: 0.0357

Gnomad4 ASJ exome AF: 0.0569

Gnomad4 EAS exome AF: 0.0609

Gnomad4 SAS exome AF: 0.0266

Gnomad4 FIN exome AF: 0.0413

Gnomad4 NFE exome AF: 0.0467

Gnomad4 OTH exome AF: 0.0455

GnomAD4 genome AF: 0.0558 AC: 6788 AN: 121624 Hom.: 506 Cov.: 18 AF XY: 0.0545 AC XY: 3214 AN XY: 58968

Gnomad4 AFR AF: 0.0701

Gnomad4 AMR AF: 0.0499

Gnomad4 ASJ AF: 0.0581

Gnomad4 EAS AF: 0.0426

Gnomad4 SAS AF: 0.0292

Gnomad4 FIN AF: 0.0436

Gnomad4 NFE AF: 0.0528

Gnomad4 OTH AF: 0.0565

Alfa AF: 0.0459 Hom.: 112

ESP6500AA AF: 0.0593 AC: 252

ESP6500EA AF: 0.0445 AC: 379

ExAC AF: 0.0432 AC: 5223

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.74
DEOGEN2	Benign	0.019	T;T;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.52	T;T;T;.;T
MetaRNN	Benign	0.0044	T;T;T;T;T
MetaSVM	Benign	-0.90	T
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.3	D;D;N;N;N
REVEL	Benign	0.064
Sift	Benign	0.095	T;T;T;T;T
Sift4G	Benign	0.077	T;T;T;T;T
Polyphen		0.15, 0.40	.;B;.;B;B
Vest4		0.13
MPC		0.69
ClinPred		0.010	T
GERP RS		-2.4
gMVP		0.17

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: rs41544112; hg19: chr6-32629920; COSMIC: COSV66574987; COSMIC: COSV66574987;