Variant chr6-32666690-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000399084.5(HLA-DQB1):c.-63-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 581,916 control chromosomes in the GnomAD database, including 5,839 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 0.20 ( 3147 hom., cov: 28)

Exomes 𝑓: 0.074 ( 2692 hom. )

Consequence

HLA-DQB1
ENST00000399084.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.804

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:

(HGNC:):

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 (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
	use as main transcript	n.32666690C>T	intergenic_region
HLA-DQB1	NM_002123.5 linkuse as main transcript	c.-83G>A	upstream_gene_variant	ENST00000434651.7	NP_002114.3	P01920Q5Y7D6Q5Y7A9
HLA-DQB1	NM_001243961.2 linkuse as main transcript	c.-83G>A	upstream_gene_variant		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.-83G>A		upstream_gene_variant		6	NM_002123.5	ENSP00000407332.2		Q5Y7D6
HLA-DQB1	ENST00000374943.8 linkuse as main transcript	c.-83G>A		upstream_gene_variant		6		ENSP00000364080.4		Q5SU54

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29534

AN:

150792

Hom.:

3145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.0816

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.204

GnomAD4 exome

AF:

0.0740

AC:

31916

AN:

431008

Hom.:

2692

Cov.:

AF XY:

0.0777

AC XY:

18148

AN XY:

233650

show subpopulations

Gnomad4 AFR exome

AF:

0.0587

Gnomad4 AMR exome

AF:

0.0397

Gnomad4 ASJ exome

AF:

0.0645

Gnomad4 EAS exome

AF:

0.0103

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.0466

Gnomad4 NFE exome

AF:

0.0759

Gnomad4 OTH exome

AF:

0.0716

GnomAD4 genome

AF:

0.196

AC:

29539

AN:

150908

Hom.:

3147

Cov.:

AF XY:

0.190

AC XY:

13990

AN XY:

73720

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.157

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.0818

Gnomad4 SAS

AF:

0.227

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.201

Alfa

AF:

0.210

Hom.:

1069

Bravo

AF:

0.203

Asia WGS

AF:

0.115

AC:

401

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.0

DANN

Benign

0.88

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