Genetic Variant HLA-DOA:c.*214C>A (chr6-33006624-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002119.4(HLA-DOA):c.*214C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 673,018 control chromosomes in the GnomAD database, including 60,142 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 0.41 ( 12761 hom., cov: 31)

Exomes 𝑓: 0.42 ( 47381 hom. )

Consequence

HLA-DOA
NM_002119.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.128

Publications

42 publications found

Variant links:

Genes affected

HLA-DOA (HGNC:4936): (major histocompatibility complex, class II, DO alpha) HLA-DOA belongs to the HLA class II alpha chain paralogues. HLA-DOA forms a heterodimer with HLA-DOB. The heterodimer, HLA-DO, is found in lysosomes in B cells and regulates HLA-DM-mediated peptide loading on MHC class II molecules. In comparison with classical HLA class II molecules, this gene exhibits very little sequence variation, especially at the protein level. [provided by RefSeq, Jul 2008]

HLA-DOA links:

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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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002119.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DOA	NM_002119.4	MANE Select	c.*214C>A		3_prime_UTR	Exon 5 of 5	NP_002110.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HLA-DOA	ENST00000229829.7	TSL:6 MANE Select	c.*214C>A	3_prime_UTR	Exon 5 of 5	ENSP00000229829.3
HLA-DOA	ENST00000490305.5	TSL:6	n.385C>A	non_coding_transcript_exon	Exon 3 of 3
HLA-DOA	ENST00000485901.1	TSL:6	n.*177C>A	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61600

AN:

151810

Hom.:

12750

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.403

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.574

Gnomad SAS

AF:

0.405

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.380

GnomAD4 exome

AF:

0.419

AC:

218519

AN:

521090

Hom.:

47381

Cov.:

AF XY:

0.419

AC XY:

116849

AN XY:

278550

show subpopulations

African (AFR)

AF:

0.339

AC:

5047

AN:

14908

American (AMR)

AF:

0.294

AC:

8908

AN:

30334

Ashkenazi Jewish (ASJ)

AF:

0.315

AC:

5275

AN:

16760

East Asian (EAS)

AF:

0.444

AC:

14116

AN:

31804

South Asian (SAS)

AF:

0.408

AC:

22294

AN:

54652

European-Finnish (FIN)

AF:

0.445

AC:

14842

AN:

33382

Middle Eastern (MID)

AF:

0.337

AC:

756

AN:

2244

European-Non Finnish (NFE)

AF:

0.439

AC:

135067

AN:

307970

Other (OTH)

AF:

0.421

AC:

12214

AN:

29036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

6289

12578

18866

25155

31444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

848

1696

2544

3392

4240

<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:

0.406

AC:

61650

AN:

151928

Hom.:

12761

Cov.:

AF XY:

0.407

AC XY:

30213

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.346

AC:

14342

AN:

41414

American (AMR)

AF:

0.360

AC:

5496

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

1086

AN:

3466

East Asian (EAS)

AF:

0.574

AC:

2955

AN:

5146

South Asian (SAS)

AF:

0.405

AC:

1948

AN:

4810

European-Finnish (FIN)

AF:

0.449

AC:

4744

AN:

10566

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.439

AC:

29807

AN:

67928

Other (OTH)

AF:

0.383

AC:

808

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1838

3676

5513

7351

9189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<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:

0.421

Hom.:

34473

Bravo

AF:

0.395

Asia WGS

AF:

0.465

AC:

1617

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.9

(source)

DANN

Benign

0.82

PhyloP100

0.13

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over