Variant rs9274384 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.319T>G(p.Leu107Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,031,444 control chromosomes in the GnomAD database, including 66,528 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.26 ( 8380 hom., cov: 18)

Exomes 𝑓: 0.23 ( 58148 hom. )

Consequence

HLA-DQB1
NM_002123.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.69

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:

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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=0.017882526).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQB1	NM_002123.5 link	c.319T>G	p.Leu107Val	missense_variant	Exon 2 of 5	ENST00000434651.7	NP_002114.3	P01920Q5Y7D6Q5Y7A9
HLA-DQB1	NM_001243961.2 link	c.319T>G	p.Leu107Val	missense_variant	Exon 2 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.319T>G	p.Leu107Val	missense_variant	Exon 2 of 5	6	NM_002123.5	ENSP00000407332.2		Q5Y7D6
HLA-DQB1	ENST00000374943.8 link	c.319T>G	p.Leu107Val	missense_variant	Exon 2 of 6	6		ENSP00000364080.4		Q5SU54

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

30901

AN:

116632

Hom.:

8373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.304

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.246

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.0860

AC:

12341

AN:

143434

Hom.:

2170

AF XY:

0.0918

AC XY:

7293

AN XY:

79446

show subpopulations

Gnomad AFR exome

AF:

0.0716

Gnomad AMR exome

AF:

0.0636

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.0893

Gnomad SAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.0862

Gnomad NFE exome

AF:

0.0789

Gnomad OTH exome

AF:

0.0816

GnomAD4 exome

AF:

0.231

AC:

211477

AN:

914738

Hom.:

58148

Cov.:

AF XY:

0.237

AC XY:

110464

AN XY:

466332

show subpopulations

Gnomad4 AFR exome

AF:

0.288

Gnomad4 AMR exome

AF:

0.227

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.221

Gnomad4 SAS exome

AF:

0.308

Gnomad4 FIN exome

AF:

0.311

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.249

GnomAD4 genome

AF:

0.265

AC:

30924

AN:

116706

Hom.:

8380

Cov.:

AF XY:

0.266

AC XY:

15033

AN XY:

56532

show subpopulations

Gnomad4 AFR

AF:

0.304

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.237

Gnomad4 EAS

AF:

0.241

Gnomad4 SAS

AF:

0.312

Gnomad4 FIN

AF:

0.338

Gnomad4 NFE

AF:

0.236

Gnomad4 OTH

AF:

0.304

Alfa

AF:

0.00275

Hom.:

ESP6500AA

AF:

0.0761

AC:

295

ESP6500EA

AF:

0.0489

AC:

394

ExAC

AF:

0.199

AC:

22807

Asia WGS

AF:

0.404

AC:

1384

AN:

3424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.0010

DANN

Benign

0.32

DEOGEN2

Benign

0.012

T;T;.;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.031

T;T;.;T

MetaRNN

Benign

0.018

T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

1.7

N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.91

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.042

MPC

0.56

ClinPred

0.011

GERP RS

-0.39

gMVP

0.099

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