Genetic Variant NM_002121.6:c.364+209A>G (chr6-33081144-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002121.6(HLA-DPB1):c.364+209A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 585,394 control chromosomes in the GnomAD database, including 17,532 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 ( 8243 hom., cov: 31)

Exomes 𝑓: 0.17 ( 9289 hom. )

Consequence

HLA-DPB1
NM_002121.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0940

Publications

25 publications found

Variant links:

Genes affected

HLA-DPB1 (HGNC:4940): (major histocompatibility complex, class II, DP beta 1) HLA-DPB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta chain (DPB), 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 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. 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-DPB1 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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6 link	c.364+209A>G		intron_variant	Intron 2 of 5	ENST00000418931.7	NP_002112.3	P04440I4EC15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPB1	ENST00000418931.7 link	c.364+209A>G		intron_variant	Intron 2 of 5	6	NM_002121.6	ENSP00000408146.2		P04440

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40650

AN:

151816

Hom.:

8220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.549

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.542

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.0911

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.272

GnomAD4 exome

AF:

0.170

AC:

73648

AN:

433460

Hom.:

9289

Cov.:

AF XY:

0.168

AC XY:

37815

AN XY:

225494

show subpopulations

African (AFR)

AF:

0.542

AC:

6366

AN:

11746

American (AMR)

AF:

0.158

AC:

2418

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

1432

AN:

12792

East Asian (EAS)

AF:

0.456

AC:

13411

AN:

29404

South Asian (SAS)

AF:

0.171

AC:

5818

AN:

34060

European-Finnish (FIN)

AF:

0.0930

AC:

2606

AN:

28030

Middle Eastern (MID)

AF:

0.120

AC:

228

AN:

1900

European-Non Finnish (NFE)

AF:

0.133

AC:

36502

AN:

275290

Other (OTH)

AF:

0.195

AC:

4867

AN:

24930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

2277

4553

6830

9106

11383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

430

860

1290

1720

2150

<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:

0.268

AC:

40702

AN:

151934

Hom.:

8243

Cov.:

AF XY:

0.262

AC XY:

19470

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.548

AC:

22646

AN:

41326

American (AMR)

AF:

0.181

AC:

2765

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

384

AN:

3472

East Asian (EAS)

AF:

0.542

AC:

2785

AN:

5134

South Asian (SAS)

AF:

0.197

AC:

951

AN:

4822

European-Finnish (FIN)

AF:

0.0911

AC:

967

AN:

10612

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.140

AC:

9508

AN:

67962

Other (OTH)

AF:

0.278

AC:

586

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1226

2451

3677

4902

6128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.176

Hom.:

2509

Bravo

AF:

0.290

Asia WGS

AF:

0.334

AC:

1160

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

6.0

(source)

DANN

Benign

0.24

PhyloP100

-0.094

PromoterAI

0.017

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