Genetic Variant ENST00000452392.2:c.1933-54G>A (chr6-32817006-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000452392.2(ENSG00000250264):c.1933-54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,333,512 control chromosomes in the GnomAD database, including 96,503 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 0.35 ( 10254 hom., cov: 32)

Exomes 𝑓: 0.37 ( 86249 hom. )

Consequence

ENSG00000250264
ENST00000452392.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.771

Publications

49 publications found

Variant links:

Genes affected

ENSG00000250264 (HGNC:):

ENSG00000250264 links:

HLA-DOB (HGNC:4937): (major histocompatibility complex, class II, DO beta) HLA-DOB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DOA) and a beta chain (DOB), both anchored in the membrane. It is located in intracellular vesicles. DO suppresses peptide loading of MHC class II molecules by inhibiting HLA-DM. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one 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. [provided by RefSeq, Jul 2008]

HLA-DOB 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DOB	NM_002120.4 link	c.-55G>A		upstream_gene_variant		ENST00000438763.7	NP_002111.1	P13765Q5QNS2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000250264	ENST00000452392.2 link	c.1933-54G>A		intron_variant	Intron 11 of 14	2		ENSP00000391806.2		E7ENX8
HLA-DOB	ENST00000438763.7 link	c.-55G>A		upstream_gene_variant		6	NM_002120.4	ENSP00000390020.2		P13765

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53813

AN:

151840

Hom.:

10247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.605

Gnomad AMR

AF:

0.407

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.535

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.499

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.375

Gnomad OTH

AF:

0.353

GnomAD4 exome

AF:

0.374

AC:

442311

AN:

1181554

Hom.:

86249

Cov.:

AF XY:

0.376

AC XY:

225897

AN XY:

600544

show subpopulations

African (AFR)

AF:

0.229

AC:

6338

AN:

27664

American (AMR)

AF:

0.471

AC:

20161

AN:

42808

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

9067

AN:

24028

East Asian (EAS)

AF:

0.491

AC:

18828

AN:

38332

South Asian (SAS)

AF:

0.443

AC:

35344

AN:

79776

European-Finnish (FIN)

AF:

0.492

AC:

25436

AN:

51718

Middle Eastern (MID)

AF:

0.350

AC:

1808

AN:

5172

European-Non Finnish (NFE)

AF:

0.356

AC:

306807

AN:

861084

Other (OTH)

AF:

0.363

AC:

18522

AN:

50972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

13126

26252

39379

52505

65631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8608

17216

25824

34432

43040

<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:

0.354

AC:

53842

AN:

151958

Hom.:

10254

Cov.:

AF XY:

0.364

AC XY:

27010

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.224

AC:

9279

AN:

41434

American (AMR)

AF:

0.407

AC:

6222

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1267

AN:

3468

East Asian (EAS)

AF:

0.534

AC:

2758

AN:

5164

South Asian (SAS)

AF:

0.455

AC:

2189

AN:

4806

European-Finnish (FIN)

AF:

0.499

AC:

5254

AN:

10536

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.375

AC:

25464

AN:

67966

Other (OTH)

AF:

0.358

AC:

754

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1732

3464

5197

6929

8661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<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:

0.364

Hom.:

26346

Bravo

AF:

0.340

Asia WGS

AF:

0.447

AC:

1554

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.3

(source)

DANN

Benign

0.61

PhyloP100

-0.77

PromoterAI

-0.15

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over