Variant rs9277471 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002121.6(HLA-DPB1):c.757+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,541,086 control chromosomes in the GnomAD database, including 84,574 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 0.38 ( 12451 hom., cov: 31)

Exomes 𝑓: 0.31 ( 72123 hom. )

Consequence

HLA-DPB1
NM_002121.6 intron

Scores

Splicing: ADA: 0.00004650

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.612

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6 linkuse as main transcript	c.757+16G>A		intron_variant		ENST00000418931.7	NP_002112.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	Appris
HLA-DPB1	ENST00000418931.7 linkuse as main transcript	c.757+16G>A		intron_variant		NM_002121.6	ENSP00000408146	P1
HLA-DPB1	ENST00000416804.1 linkuse as main transcript	c.674G>A	p.Arg225Lys	missense_variant, splice_region_variant	3/5		ENSP00000399832
HLA-DPB1	ENST00000428835.5 linkuse as main transcript			downstream_gene_variant			ENSP00000412654

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57795

AN:

151906

Hom.:

12428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.185

Gnomad EAS

AF:

0.639

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.385

GnomAD3 exomes

AF:

0.321

AC:

77744

AN:

242002

Hom.:

14425

AF XY:

0.317

AC XY:

41320

AN XY:

130482

show subpopulations

Gnomad AFR exome

AF:

0.572

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.194

Gnomad EAS exome

AF:

0.633

Gnomad SAS exome

AF:

0.316

Gnomad FIN exome

AF:

0.256

Gnomad NFE exome

AF:

0.290

Gnomad OTH exome

AF:

0.296

GnomAD4 exome

AF:

0.313

AC:

434480

AN:

1389060

Hom.:

72123

Cov.:

AF XY:

0.311

AC XY:

215559

AN XY:

694176

show subpopulations

Gnomad4 AFR exome

AF:

0.582

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.597

Gnomad4 SAS exome

AF:

0.313

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.302

Gnomad4 OTH exome

AF:

0.330

GnomAD4 genome

AF:

0.381

AC:

57846

AN:

152026

Hom.:

12451

Cov.:

AF XY:

0.374

AC XY:

27778

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.569

Gnomad4 AMR

AF:

0.300

Gnomad4 ASJ

AF:

0.185

Gnomad4 EAS

AF:

0.640

Gnomad4 SAS

AF:

0.339

Gnomad4 FIN

AF:

0.253

Gnomad4 NFE

AF:

0.300

Gnomad4 OTH

AF:

0.394

Alfa

AF:

0.305

Hom.:

12421

Bravo

AF:

0.390

Asia WGS

AF:

0.488

AC:

1695

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000047

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.71

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.71

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over