dbSNP rs7990: HLA-DQA1:p.Ala183Asp (chr6-32642188-C-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_002122.5(HLA-DQA1):c.548C>A(p.Ala183Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 1,321,916 control chromosomes in the GnomAD database, including 5,811 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.013 ( 17 hom., cov: 16)

Exomes 𝑓: 0.049 ( 5794 hom. )

Consequence

HLA-DQA1
NM_002122.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.51

Publications

21 publications found

Variant links:

Genes affected

HLA-DQA1 (HGNC:4942): (major histocompatibility complex, class II, DQ alpha 1) HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The 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 alpha chain is approximately 33-35 kDa. It is encoded by 5 exons; exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and 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. [provided by RefSeq, Jul 2008]

HLA-DQA1 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 (MetaRNN=0.0022338629).

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5 link	c.548C>A	p.Ala183Asp	missense_variant	Exon 3 of 5	ENST00000343139.11	NP_002113.2	P01909A0A173ADG5Q8MH44
HLA-DQA1	XM_006715079.5 link	c.548C>A	p.Ala183Asp	missense_variant	Exon 3 of 4		XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11 link	c.548C>A	p.Ala183Asp	missense_variant	Exon 3 of 5	6	NM_002122.5	ENSP00000339398.5		P01909

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1249

AN:

99782

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.0238

Gnomad AMR

AF:

0.00817

Gnomad ASJ

AF:

0.00769

Gnomad EAS

AF:

0.0384

Gnomad SAS

AF:

0.00375

Gnomad FIN

AF:

0.00764

Gnomad MID

AF:

0.0118

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.0662

AC:

15811

AN:

238892

AF XY:

0.0635

show subpopulations

Gnomad AFR exome

AF:

0.0722

Gnomad AMR exome

AF:

0.0352

Gnomad ASJ exome

AF:

0.0270

Gnomad EAS exome

AF:

0.201

Gnomad FIN exome

AF:

0.0733

Gnomad NFE exome

AF:

0.0705

Gnomad OTH exome

AF:

0.0593

GnomAD4 exome

AF:

0.0492

AC:

60075

AN:

1222044

Hom.:

5794

Cov.:

AF XY:

0.0478

AC XY:

29374

AN XY:

614234

show subpopulations

African (AFR)

AF:

0.0395

AC:

1122

AN:

28426

American (AMR)

AF:

0.0321

AC:

1353

AN:

42118

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

480

AN:

23776

East Asian (EAS)

AF:

0.151

AC:

4711

AN:

31216

South Asian (SAS)

AF:

0.0119

AC:

984

AN:

82486

European-Finnish (FIN)

AF:

0.0386

AC:

1827

AN:

47312

Middle Eastern (MID)

AF:

0.0294

AC:

143

AN:

4872

European-Non Finnish (NFE)

AF:

0.0518

AC:

47154

AN:

910566

Other (OTH)

AF:

0.0449

AC:

2301

AN:

51272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.409

Heterozygous variant carriers

2044

4088

6131

8175

10219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1700

3400

5100

6800

8500

<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:

0.0125

AC:

1253

AN:

99872

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

602

AN XY:

48658

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0124

AC:

347

AN:

27968

American (AMR)

AF:

0.00828

AC:

AN:

8696

Ashkenazi Jewish (ASJ)

AF:

0.00769

AC:

AN:

2340

East Asian (EAS)

AF:

0.0386

AC:

104

AN:

2696

South Asian (SAS)

AF:

0.00375

AC:

AN:

3466

European-Finnish (FIN)

AF:

0.00764

AC:

AN:

7070

Middle Eastern (MID)

AF:

0.0122

AC:

AN:

164

European-Non Finnish (NFE)

AF:

0.0135

AC:

615

AN:

45534

Other (OTH)

AF:

0.00994

AC:

AN:

1308

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.300

Heterozygous variant carriers

108

215

323

430

538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0569

Hom.:

ESP6500AA

AF:

0.0775

AC:

234

ESP6500EA

AF:

0.0843

AC:

456

ExAC

AF:

0.0768

AC:

9000

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.3

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.011

.;.;T;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.35

.;.;T;T

MetaRNN

Benign

0.0022

T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

-1.5

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.1

N;N;N;N

REVEL

Benign

0.049

Sift

Benign

0.52

T;T;T;T

Sift4G

Benign

0.54

T;T;T;T

Vest4

0.064

MPC

1.2

ClinPred

0.0043

GERP RS

-2.0

gMVP

0.40

Mutation Taster

=97/3

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