Variant rs41544112 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.502

Variant links:

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]

HLA-DQB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 link	c.485G>A	p.Arg162Gln	missense_variant	Exon 3 of 5	ENST00000434651.7	NP_002114.3	P01920Q5Y7D6Q5Y7A9
HLA-DQB1	NM_001243961.2 link	c.485G>A	p.Arg162Gln	missense_variant	Exon 3 of 6		NP_001230890.1	Q5SU54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQB1	ENST00000434651.7 link	c.485G>A	p.Arg162Gln	missense_variant	Exon 3 of 5	6	NM_002123.5	ENSP00000407332.2		Q5Y7D6
HLA-DQB1	ENST00000374943.8 link	c.485G>A	p.Arg162Gln	missense_variant	Exon 3 of 6	6		ENSP00000364080.4		Q5SU54

Frequencies

GnomAD3 genomes

AF:

0.0558

AC:

6777

AN:

121520

Hom.:

505

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0451

AC XY:

30111

AN XY:

668254

show subpopulations

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.:

AF XY:

0.0545

AC XY:

3214

AN XY:

58968

show subpopulations

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

BayesDel_noAF

Benign

-0.49

CADD

Benign

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

LIST_S2

Benign

0.52

T;T;T;.;T

MetaRNN

Benign

0.0044

T;T;T;T;T

MetaSVM

Benign

-0.90

PrimateAI

Benign

0.25

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over