Genetic Variant NM_002121.6:c.364+1312C>A (chr6-33082247-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_002121.6(HLA-DPB1):c.364+1312C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 151,618 control chromosomes in the GnomAD database, including 11,970 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 0.37 ( 11968 hom., cov: 31)

Exomes 𝑓: 0.29 ( 2 hom. )

Consequence

HLA-DPB1
NM_002121.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.114

Publications

10 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002121.6. 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-DPB1	NM_002121.6	MANE Select	c.364+1312C>A		intron	N/A	NP_002112.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HLA-DPB1	ENST00000418931.7	TSL:6 MANE Select	c.364+1312C>A	intron	N/A	ENSP00000408146.2
HLA-DPB1	ENST00000966804.1		c.365-33C>A	intron	N/A	ENSP00000636863.1
HLA-DPB1	ENST00000907475.1		c.364+1312C>A	intron	N/A	ENSP00000577534.1

Frequencies

GnomAD3 genomes

AF:

0.374

AC:

56635

AN:

151462

Hom.:

11946

Cov.:

show subpopulations

Gnomad AFR

AF:

0.561

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.294

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.646

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.381

GnomAD4 exome

AF:

0.289

AC:

AN:

Hom.:

AF XY:

0.292

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.273

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.374

AC:

56680

AN:

151580

Hom.:

11968

Cov.:

AF XY:

0.367

AC XY:

27185

AN XY:

74052

show subpopulations

African (AFR)

AF:

0.560

AC:

23105

AN:

41248

American (AMR)

AF:

0.294

AC:

4474

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.178

AC:

618

AN:

3466

East Asian (EAS)

AF:

0.646

AC:

3318

AN:

5138

South Asian (SAS)

AF:

0.341

AC:

1638

AN:

4802

European-Finnish (FIN)

AF:

0.247

AC:

2599

AN:

10524

Middle Eastern (MID)

AF:

0.250

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.293

AC:

19904

AN:

67854

Other (OTH)

AF:

0.389

AC:

821

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1612

3224

4835

6447

8059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<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:

0.291

Hom.:

2910

Bravo

AF:

0.385

Asia WGS

AF:

0.486

AC:

1690

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.4

(source)

DANN

Benign

0.68

PhyloP100

-0.11

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