Variant 6-32662025-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002123.5(HLA-DQB1):c.603T>C(p.Asp201Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 1,277,456 control chromosomes in the GnomAD database, including 250,456 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 0.55 ( 21923 hom., cov: 23)

Exomes 𝑓: 0.58 ( 228533 hom. )

Consequence

HLA-DQB1
NM_002123.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP7

Synonymous conserved (PhyloP=-1.47 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 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.603T>C	p.Asp201Asp	synonymous_variant	3/5	ENST00000434651.7	NP_002114.3	P01920Q5Y7D6Q5Y7A9
HLA-DQB1	NM_001243961.2 linkuse as main transcript	c.603T>C	p.Asp201Asp	synonymous_variant	3/6		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.603T>C	p.Asp201Asp	synonymous_variant	3/5	6	NM_002123.5	ENSP00000407332.2		Q5Y7D6
HLA-DQB1	ENST00000374943.8 linkuse as main transcript	c.603T>C	p.Asp201Asp	synonymous_variant	3/6	6		ENSP00000364080.4		Q5SU54

Frequencies

GnomAD3 genomes

AF:

0.551

AC:

73641

AN:

133706

Hom.:

21923

Cov.:

show subpopulations

Gnomad AFR

AF:

0.476

Gnomad AMI

AF:

0.533

Gnomad AMR

AF:

0.614

Gnomad ASJ

AF:

0.662

Gnomad EAS

AF:

0.703

Gnomad SAS

AF:

0.643

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.735

Gnomad NFE

AF:

0.574

Gnomad OTH

AF:

0.573

GnomAD3 exomes

AF:

0.622

AC:

144698

AN:

232662

Hom.:

47662

AF XY:

0.623

AC XY:

78949

AN XY:

126750

show subpopulations

Gnomad AFR exome

AF:

0.490

Gnomad AMR exome

AF:

0.779

Gnomad ASJ exome

AF:

0.678

Gnomad EAS exome

AF:

0.731

Gnomad SAS exome

AF:

0.678

Gnomad FIN exome

AF:

0.508

Gnomad NFE exome

AF:

0.581

Gnomad OTH exome

AF:

0.600

GnomAD4 exome

AF:

0.576

AC:

658676

AN:

1143664

Hom.:

228533

Cov.:

AF XY:

0.579

AC XY:

332981

AN XY:

574962

show subpopulations

Gnomad4 AFR exome

AF:

0.438

Gnomad4 AMR exome

AF:

0.720

Gnomad4 ASJ exome

AF:

0.649

Gnomad4 EAS exome

AF:

0.739

Gnomad4 SAS exome

AF:

0.656

Gnomad4 FIN exome

AF:

0.466

Gnomad4 NFE exome

AF:

0.565

Gnomad4 OTH exome

AF:

0.573

GnomAD4 genome

AF:

0.551

AC:

73674

AN:

133792

Hom.:

21923

Cov.:

AF XY:

0.548

AC XY:

35353

AN XY:

64558

show subpopulations

Gnomad4 AFR

AF:

0.476

Gnomad4 AMR

AF:

0.615

Gnomad4 ASJ

AF:

0.662

Gnomad4 EAS

AF:

0.704

Gnomad4 SAS

AF:

0.641

Gnomad4 FIN

AF:

0.447

Gnomad4 NFE

AF:

0.574

Gnomad4 OTH

AF:

0.571

Alfa

AF:

0.593

Hom.:

7217

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.31

DANN

Benign

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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