Genetic Variant HLA-DPA1:c.347-110G>C (chr6-33069410-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000692443.1(HLA-DPA1):c.347-110G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,158,104 control chromosomes in the GnomAD database, including 29,791 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 0.29 ( 8535 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21256 hom. )

Consequence

HLA-DPA1
ENST00000692443.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.274

Publications

12 publications found

Variant links:

Genes affected

HLA-DPA1 (HGNC:4938): (major histocompatibility complex, class II, DP alpha 1) HLA-DPA1 belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta (DPB) chain, 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 and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DP molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules. [provided by RefSeq, Jul 2008]

HLA-DPA1 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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
HLA-DPA1	NM_001242524.2 link	c.347-110G>C	intron_variant	Intron 3 of 5	NP_001229453.1
HLA-DPA1	NM_001242525.2 link	c.347-110G>C	intron_variant	Intron 3 of 5	NP_001229454.1
HLA-DPA1	NM_001405020.1 link	c.347-110G>C	intron_variant	Intron 2 of 3	NP_001391949.1
HLA-DPA1	NM_033554.4 link	c.347-110G>C	intron_variant	Intron 2 of 4	NP_291032.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPA1	ENST00000692443.1 link	c.347-110G>C		intron_variant	Intron 2 of 4			ENSP00000509163.1		P20036

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44297

AN:

151918

Hom.:

8516

Cov.:

show subpopulations

Gnomad AFR

AF:

0.498

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.691

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.191

Gnomad NFE

AF:

0.179

Gnomad OTH

AF:

0.306

GnomAD4 exome

AF:

0.170

AC:

170691

AN:

1006066

Hom.:

21256

Cov.:

AF XY:

0.175

AC XY:

88767

AN XY:

507092

show subpopulations

African (AFR)

AF:

0.456

AC:

9278

AN:

20352

American (AMR)

AF:

0.175

AC:

5236

AN:

30002

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

2897

AN:

18222

East Asian (EAS)

AF:

0.624

AC:

22204

AN:

35594

South Asian (SAS)

AF:

0.299

AC:

18489

AN:

61916

European-Finnish (FIN)

AF:

0.103

AC:

4942

AN:

48006

Middle Eastern (MID)

AF:

0.195

AC:

871

AN:

4470

European-Non Finnish (NFE)

AF:

0.132

AC:

97983

AN:

743580

Other (OTH)

AF:

0.200

AC:

8791

AN:

43924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.414

Heterozygous variant carriers

5958

11916

17873

23831

29789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2832

5664

8496

11328

14160

<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:

0.292

AC:

44348

AN:

152038

Hom.:

8535

Cov.:

AF XY:

0.289

AC XY:

21486

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.497

AC:

20593

AN:

41416

American (AMR)

AF:

0.248

AC:

3787

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

589

AN:

3472

East Asian (EAS)

AF:

0.691

AC:

3573

AN:

5168

South Asian (SAS)

AF:

0.349

AC:

1679

AN:

4810

European-Finnish (FIN)

AF:

0.104

AC:

1100

AN:

10610

Middle Eastern (MID)

AF:

0.195

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.179

AC:

12180

AN:

67960

Other (OTH)

AF:

0.313

AC:

660

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1405

2809

4214

5618

7023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.0859

Hom.:

109

Bravo

AF:

0.310

Asia WGS

AF:

0.460

AC:

1597

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.5

(source)

DANN

Benign

0.72

PhyloP100

0.27

PromoterAI

-0.0036

Neutral

(source)

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