Variant 6-33085221-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002121.6(HLA-DPB1):c.636C>T(p.Thr212=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0061 in 1,603,186 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 49 hom. )

Consequence

HLA-DPB1
NM_002121.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.80

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 6-33085221-C-T is Benign according to our data. Variant chr6-33085221-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656482.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.8 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DPB1	NM_002121.6 linkuse as main transcript	c.636C>T	p.Thr212=	synonymous_variant	3/6	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.636C>T	p.Thr212=	synonymous_variant	3/6	NM_002121.6	ENSP00000408146	P1
HLA-DPB1	ENST00000416804.1 linkuse as main transcript	c.537C>T	p.Thr179=	synonymous_variant	2/5		ENSP00000399832
HLA-DPB1	ENST00000428835.5 linkuse as main transcript	c.567C>T	p.Thr189=	synonymous_variant	3/4		ENSP00000412654
HLA-DPB1	ENST00000498038.1 linkuse as main transcript	n.765C>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.00601

AC:

914

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00430

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00704

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00664

AC:

1611

AN:

242472

Hom.:

AF XY:

0.00663

AC XY:

875

AN XY:

131902

show subpopulations

Gnomad AFR exome

AF:

0.00407

Gnomad AMR exome

AF:

0.00425

Gnomad ASJ exome

AF:

0.0228

Gnomad EAS exome

AF:

0.00104

Gnomad SAS exome

AF:

0.00825

Gnomad FIN exome

AF:

0.00563

Gnomad NFE exome

AF:

0.00699

Gnomad OTH exome

AF:

0.00786

GnomAD4 exome

AF:

0.00611

AC:

8864

AN:

1450926

Hom.:

Cov.:

AF XY:

0.00625

AC XY:

4507

AN XY:

721470

show subpopulations

Gnomad4 AFR exome

AF:

0.00434

Gnomad4 AMR exome

AF:

0.00433

Gnomad4 ASJ exome

AF:

0.0208

Gnomad4 EAS exome

AF:

0.000404

Gnomad4 SAS exome

AF:

0.00784

Gnomad4 FIN exome

AF:

0.00514

Gnomad4 NFE exome

AF:

0.00597

Gnomad4 OTH exome

AF:

0.00698

GnomAD4 genome

AF:

0.00600

AC:

914

AN:

152260

Hom.:

Cov.:

AF XY:

0.00563

AC XY:

419

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00428

Gnomad4 AMR

AF:

0.00569

Gnomad4 ASJ

AF:

0.0231

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.00433

Gnomad4 NFE

AF:

0.00704

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00703

Hom.:

Bravo

AF:

0.00572

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

HLA-DPB1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.4

DANN

Benign

0.68

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over