dbSNP rs365066: HLA-DOA:p.Leu148Leu (chr6-33007480-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_002119.4(HLA-DOA):c.444G>A(p.Leu148Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,612,352 control chromosomes in the GnomAD database, including 143,730 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 0.40 ( 12288 hom., cov: 32)

Exomes 𝑓: 0.42 ( 131442 hom. )

Consequence

HLA-DOA
NM_002119.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0810

Publications

32 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP7

Synonymous conserved (PhyloP=-0.081 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DOA	NM_002119.4 link	c.444G>A	p.Leu148Leu	synonymous_variant	Exon 3 of 5	ENST00000229829.7	NP_002110.1	P06340X5CF87A0A1V0E3Q8A0A1V0E3Q5A0A1V0E3N1A0A1V0E3M7A0A1V0E3R3A0A1V0E3S6A0A1V0E3T1A0A1V0E3P8A0A1V0E3Q2A0A1V0E3P6A0A1V0E3S7A0A1V0E3P1A0A1V0E3Q6A0A1V0E3P3A0A1V0E3R6A0A1V0E3P9A0A1V0E3N7A0A1V0E3S0A0A1V0E3Q1A0A1V0E3N3A0A1V0E3Q4A0A1V0E3R4A0A1V0E3P0A0A1V0E3R0A0A1V0E3N6A0A1V0E3R8A0A1V0E3S4A0A1V0E3Q7A0A1V0E3Q3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DOA	ENST00000229829.7 link	c.444G>A	p.Leu148Leu	synonymous_variant	Exon 3 of 5	6	NM_002119.4	ENSP00000229829.3		P06340

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60452

AN:

152020

Hom.:

12277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.475

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.570

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.364

GnomAD2 exomes

AF:

0.397

AC:

97712

AN:

246086

AF XY:

0.403

show subpopulations

Gnomad AFR exome

AF:

0.338

Gnomad AMR exome

AF:

0.255

Gnomad ASJ exome

AF:

0.275

Gnomad EAS exome

AF:

0.583

Gnomad FIN exome

AF:

0.445

Gnomad NFE exome

AF:

0.430

Gnomad OTH exome

AF:

0.380

GnomAD4 exome

AF:

0.420

AC:

613863

AN:

1460214

Hom.:

131442

Cov.:

AF XY:

0.420

AC XY:

304758

AN XY:

726414

show subpopulations

African (AFR)

AF:

0.337

AC:

11278

AN:

33478

American (AMR)

AF:

0.268

AC:

11974

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

7291

AN:

26080

East Asian (EAS)

AF:

0.469

AC:

18607

AN:

39700

South Asian (SAS)

AF:

0.369

AC:

31780

AN:

86178

European-Finnish (FIN)

AF:

0.447

AC:

23366

AN:

52286

Middle Eastern (MID)

AF:

0.338

AC:

1948

AN:

5766

European-Non Finnish (NFE)

AF:

0.434

AC:

482387

AN:

1111716

Other (OTH)

AF:

0.418

AC:

25232

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

21394

42788

64181

85575

106969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14630

29260

43890

58520

73150

<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:

0.398

AC:

60505

AN:

152138

Hom.:

12288

Cov.:

AF XY:

0.399

AC XY:

29645

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.346

AC:

14360

AN:

41512

American (AMR)

AF:

0.344

AC:

5261

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.275

AC:

953

AN:

3468

East Asian (EAS)

AF:

0.570

AC:

2942

AN:

5158

South Asian (SAS)

AF:

0.380

AC:

1833

AN:

4824

European-Finnish (FIN)

AF:

0.451

AC:

4780

AN:

10592

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.428

AC:

29077

AN:

67976

Other (OTH)

AF:

0.366

AC:

774

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1910

3820

5731

7641

9551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<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:

0.406

Hom.:

17259

Bravo

AF:

0.387

Asia WGS

AF:

0.443

AC:

1543

AN:

3478

EpiCase

AF:

0.406

EpiControl

AF:

0.406

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.6

(source)

DANN

Benign

0.74

PhyloP100

-0.081

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over