dbSNP rs143352256: HLA-DPB1:c.100+8C>T (chr6-33076149-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002121.6(HLA-DPB1):c.100+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,579,764 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 34 hom. )

Consequence

HLA-DPB1
NM_002121.6 splice_region, intron

Scores

Splicing: ADA: 0.00002491

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.148

Publications

0 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:

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 6-33076149-C-T is Benign according to our data. Variant chr6-33076149-C-T is described in ClinVar as Benign. ClinVar VariationId is 725738.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00356 (542/152306) while in subpopulation EAS AF = 0.0255 (132/5178). AF 95% confidence interval is 0.022. There are 3 homozygotes in GnomAd4. There are 281 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HLA-DPB1	NM_002121.6	MANE Select	c.100+8C>T	splice_region intron	N/A	NP_002112.3
HLA-DPA1	NM_001242524.2		c.-99-2480G>A	intron	N/A	NP_001229453.1	P20036
HLA-DPA1	NM_001242525.2		c.-23-2556G>A	intron	N/A	NP_001229454.1	X5CKE2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HLA-DPB1	ENST00000418931.7	TSL:6 MANE Select	c.100+8C>T	splice_region intron	N/A	ENSP00000408146.2	P04440
HLA-DPB1	ENST00000966804.1		c.100+8C>T	splice_region intron	N/A	ENSP00000636863.1
HLA-DPA1	ENST00000419277.5	TSL:6	c.-99-2480G>A	intron	N/A	ENSP00000393566.1	P20036

Frequencies

GnomAD3 genomes

AF:

0.00354

AC:

539

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00830

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0256

Gnomad SAS

AF:

0.00806

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00312

AC:

707

AN:

226376

AF XY:

0.00323

show subpopulations

Gnomad AFR exome

AF:

0.00674

Gnomad AMR exome

AF:

0.000838

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0240

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000496

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00104

AC:

1482

AN:

1427458

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

867

AN XY:

710948

show subpopulations

African (AFR)

AF:

0.00669

AC:

220

AN:

32868

American (AMR)

AF:

0.000899

AC:

AN:

43376

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25692

East Asian (EAS)

AF:

0.0116

AC:

455

AN:

39360

South Asian (SAS)

AF:

0.00606

AC:

510

AN:

84118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51750

Middle Eastern (MID)

AF:

0.000700

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.0000240

AC:

AN:

1085412

Other (OTH)

AF:

0.00385

AC:

228

AN:

59164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

106

160

213

266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00356

AC:

542

AN:

152306

Hom.:

Cov.:

AF XY:

0.00377

AC XY:

281

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00835

AC:

347

AN:

41558

American (AMR)

AF:

0.000915

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0255

AC:

132

AN:

5178

South Asian (SAS)

AF:

0.00807

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68022

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

105

131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.00390

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.1

(source)

DANN

Benign

0.78

PhyloP100

0.15

PromoterAI

-0.051

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000025

dbscSNV1_RF

Benign

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over