Genetic Variant NM_002120.4:c.*269C>T (chr6-32812947-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 NM_002120.4(HLA-DOB):c.*269C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 547,764 control chromosomes in the GnomAD database, including 22,864 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 0.27 ( 5777 hom., cov: 31)

Exomes 𝑓: 0.29 ( 17087 hom. )

Consequence

HLA-DOB
NM_002120.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

Publications

54 publications found

Variant links:

Genes affected

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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DOB	NM_002120.4 link	c.*269C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000438763.7	NP_002111.1	P13765Q5QNS2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DOB	ENST00000438763.7 link	c.*269C>T		3_prime_UTR_variant	Exon 6 of 6	6	NM_002120.4	ENSP00000390020.2		P13765

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41416

AN:

151898

Hom.:

5777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.281

Gnomad AMI

AF:

0.213

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.302

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.277

Gnomad OTH

AF:

0.280

GnomAD4 exome

AF:

0.286

AC:

112996

AN:

395748

Hom.:

17087

Cov.:

AF XY:

0.291

AC XY:

60257

AN XY:

207388

show subpopulations

African (AFR)

AF:

0.278

AC:

3224

AN:

11596

American (AMR)

AF:

0.202

AC:

3277

AN:

16252

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

4149

AN:

12490

East Asian (EAS)

AF:

0.311

AC:

8746

AN:

28150

South Asian (SAS)

AF:

0.325

AC:

12155

AN:

37376

European-Finnish (FIN)

AF:

0.276

AC:

7032

AN:

25454

Middle Eastern (MID)

AF:

0.365

AC:

654

AN:

1792

European-Non Finnish (NFE)

AF:

0.281

AC:

67219

AN:

239190

Other (OTH)

AF:

0.279

AC:

6540

AN:

23448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

3615

7230

10846

14461

18076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.273

AC:

41428

AN:

152016

Hom.:

5777

Cov.:

AF XY:

0.272

AC XY:

20183

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.281

AC:

11653

AN:

41448

American (AMR)

AF:

0.216

AC:

3297

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.326

AC:

1129

AN:

3466

East Asian (EAS)

AF:

0.248

AC:

1283

AN:

5164

South Asian (SAS)

AF:

0.301

AC:

1452

AN:

4822

European-Finnish (FIN)

AF:

0.276

AC:

2916

AN:

10556

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.277

AC:

18797

AN:

67972

Other (OTH)

AF:

0.280

AC:

591

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1518

3036

4555

6073

7591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.288

Hom.:

26966

Bravo

AF:

0.266

Asia WGS

AF:

0.272

AC:

948

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.19

(source)

DANN

Benign

0.69

PhyloP100

-1.2

Mutation Taster

=100/0

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

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