dbSNP rs2647025: HLA-DQB1:c.-64+96C>T (chr6-32668172-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000399084.5(HLA-DQB1):c.-64+96C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,668 control chromosomes in the GnomAD database, including 6,086 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 0.28 ( 6027 hom., cov: 31)

Exomes 𝑓: 0.35 ( 59 hom. )

Consequence

HLA-DQB1
ENST00000399084.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.244

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQB1	ENST00000399084.5 link	c.-64+96C>T		intron_variant	Intron 1 of 5	6		ENSP00000382034.1		Q5Y7D6

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41776

AN:

151726

Hom.:

6020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.353

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.279

GnomAD4 exome

AF:

0.346

AC:

285

AN:

824

Hom.:

AF XY:

0.328

AC XY:

135

AN XY:

412

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.192

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.382

AC:

237

AN:

620

European-Non Finnish (NFE)

AF:

0.256

AC:

AN:

Other (OTH)

AF:

0.227

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.275

AC:

41812

AN:

151844

Hom.:

6027

Cov.:

AF XY:

0.279

AC XY:

20733

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.221

AC:

9135

AN:

41400

American (AMR)

AF:

0.383

AC:

5845

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1093

AN:

3460

East Asian (EAS)

AF:

0.354

AC:

1823

AN:

5144

South Asian (SAS)

AF:

0.254

AC:

1222

AN:

4806

European-Finnish (FIN)

AF:

0.323

AC:

3404

AN:

10536

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.269

AC:

18270

AN:

67914

Other (OTH)

AF:

0.277

AC:

582

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

1356

2713

4069

5426

6782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

432

864

1296

1728

2160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.277

Hom.:

12061

Bravo

AF:

0.287

Asia WGS

AF:

0.229

AC:

797

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.5

(source)

DANN

Benign

0.37

PhyloP100

0.24

PromoterAI

-0.0030

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over