Variant 6-32661360-T-G 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.759A>C(p.Gln253His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,057,032 control chromosomes in the GnomAD database, including 169,105 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 17966 hom., cov: 20)

Exomes 𝑓: 0.49 ( 151139 hom. )

Consequence

HLA-DQB1
NM_002123.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.250

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:

HLA-DQB1 (HGNC:):

HLA-DQB1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011523664).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQB1	NM_002123.5 linkuse as main transcript	c.759A>C	p.Gln253His	missense_variant	4/5	ENST00000434651.7	NP_002114.3	P01920Q5Y7D6Q5Y7A9
HLA-DQB1	NM_001243961.2 linkuse as main transcript	c.759A>C	p.Gln253His	missense_variant	4/6		NP_001230890.1	Q5SU54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQB1	ENST00000434651.7 linkuse as main transcript	c.759A>C	p.Gln253His	missense_variant	4/5	6	NM_002123.5	ENSP00000407332.2		Q5Y7D6
HLA-DQB1	ENST00000374943.8 linkuse as main transcript	c.759A>C	p.Gln253His	missense_variant	4/6	6		ENSP00000364080.4		Q5SU54

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

61557

AN:

121302

Hom.:

17962

Cov.:

show subpopulations

Gnomad AFR

AF:

0.465

Gnomad AMI

AF:

0.508

Gnomad AMR

AF:

0.558

Gnomad ASJ

AF:

0.567

Gnomad EAS

AF:

0.511

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.679

Gnomad NFE

AF:

0.540

Gnomad OTH

AF:

0.536

GnomAD3 exomes

AF:

0.204

AC:

27126

AN:

133128

Hom.:

9334

AF XY:

0.212

AC XY:

15528

AN XY:

73274

show subpopulations

Gnomad AFR exome

AF:

0.137

Gnomad AMR exome

AF:

0.249

Gnomad ASJ exome

AF:

0.291

Gnomad EAS exome

AF:

0.0961

Gnomad SAS exome

AF:

0.311

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.216

GnomAD4 exome

AF:

0.488

AC:

456721

AN:

935656

Hom.:

151139

Cov.:

AF XY:

0.488

AC XY:

230231

AN XY:

471482

show subpopulations

Gnomad4 AFR exome

AF:

0.419

Gnomad4 AMR exome

AF:

0.706

Gnomad4 ASJ exome

AF:

0.555

Gnomad4 EAS exome

AF:

0.429

Gnomad4 SAS exome

AF:

0.470

Gnomad4 FIN exome

AF:

0.398

Gnomad4 NFE exome

AF:

0.488

Gnomad4 OTH exome

AF:

0.488

GnomAD4 genome

AF:

0.507

AC:

61584

AN:

121376

Hom.:

17966

Cov.:

AF XY:

0.498

AC XY:

29096

AN XY:

58440

show subpopulations

Gnomad4 AFR

AF:

0.465

Gnomad4 AMR

AF:

0.559

Gnomad4 ASJ

AF:

0.567

Gnomad4 EAS

AF:

0.511

Gnomad4 SAS

AF:

0.435

Gnomad4 FIN

AF:

0.385

Gnomad4 NFE

AF:

0.540

Gnomad4 OTH

AF:

0.531

Alfa

AF:

0.578

Hom.:

11083

ExAC

AF:

0.245

AC:

23958

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.043

DANN

Benign

0.78

DEOGEN2

Benign

0.0037

T;.;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.51

T;.;T

MetaRNN

Benign

0.0012

T;T;T

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.24

PROVEAN

Benign

1.7

N;N;N

REVEL

Benign

0.027

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.19

MutPred

0.26

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MPC

0.52

ClinPred

0.00067

GERP RS

1.9

gMVP

0.26

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