dbSNP rs1140343: HLA-DQB1:p.Gln253Gln (chr6-32661360-T-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_002123.5(HLA-DQB1):c.759A>G(p.Gln253Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HLA-DQB1
NM_002123.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.250

Publications

25 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP7

Synonymous conserved (PhyloP=-0.25 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQB1	NM_002123.5 link	c.759A>G	p.Gln253Gln	synonymous_variant	Exon 4 of 5	ENST00000434651.7	NP_002114.3	P01920Q5Y7D6Q5Y7A9
HLA-DQB1	NM_001243961.2 link	c.759A>G	p.Gln253Gln	synonymous_variant	Exon 4 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.759A>G	p.Gln253Gln	synonymous_variant	Exon 4 of 5	6	NM_002123.5	ENSP00000407332.2		Q5Y7D6
HLA-DQB1	ENST00000374943.8 link	c.759A>G	p.Gln253Gln	synonymous_variant	Exon 4 of 6	6		ENSP00000364080.4		Q5SU54

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

134022

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1163056

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

584672

African (AFR)

AF:

0.00

AC:

AN:

28750

American (AMR)

AF:

0.00

AC:

AN:

35048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21448

East Asian (EAS)

AF:

0.00

AC:

AN:

30234

South Asian (SAS)

AF:

0.00

AC:

AN:

77242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45908

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3540

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

871292

Other (OTH)

AF:

0.00

AC:

AN:

49594

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

134022

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64582

African (AFR)

AF:

0.00

AC:

AN:

37382

American (AMR)

AF:

0.00

AC:

AN:

11994

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3018

East Asian (EAS)

AF:

0.00

AC:

AN:

4088

South Asian (SAS)

AF:

0.00

AC:

AN:

4052

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62038

Other (OTH)

AF:

0.00

AC:

AN:

1830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.88

(source)

DANN

Benign

0.78

PhyloP100

-0.25

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over