Variant 6-32816899-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002120.4(HLA-DOB):c.53G>A(p.Arg18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0532 in 1,612,446 control chromosomes in the GnomAD database, including 3,344 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.083 ( 758 hom., cov: 32)

Exomes 𝑓: 0.050 ( 2586 hom. )

Consequence

HLA-DOB
NM_002120.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.538

Variant links:

Genes affected

HLA-DOB (HGNC:4937): (major histocompatibility complex, class II, DO beta) HLA-DOB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DOA) and a beta chain (DOB), both anchored in the membrane. It is located in intracellular vesicles. DO suppresses peptide loading of MHC class II molecules by inhibiting HLA-DM. 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. [provided by RefSeq, Jul 2008]

HLA-DOB 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 (MetaRNN=0.0018908381).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DOB	NM_002120.4 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant	1/6	ENST00000438763.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DOB	ENST00000438763.7 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant	1/6		NM_002120.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0825

AC:

12539

AN:

151956

Hom.:

756

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0567

Gnomad ASJ

AF:

0.0611

Gnomad EAS

AF:

0.0613

Gnomad SAS

AF:

0.0931

Gnomad FIN

AF:

0.0626

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0403

Gnomad OTH

AF:

0.0783

GnomAD3 exomes

AF:

0.0619

AC:

15251

AN:

246484

Hom.:

629

AF XY:

0.0632

AC XY:

8494

AN XY:

134306

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.0377

Gnomad ASJ exome

AF:

0.0626

Gnomad EAS exome

AF:

0.0401

Gnomad SAS exome

AF:

0.0951

Gnomad FIN exome

AF:

0.0633

Gnomad NFE exome

AF:

0.0489

Gnomad OTH exome

AF:

0.0629

GnomAD4 exome

AF:

0.0502

AC:

73275

AN:

1460372

Hom.:

2586

Cov.:

AF XY:

0.0518

AC XY:

37598

AN XY:

726524

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.0414

Gnomad4 ASJ exome

AF:

0.0622

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.0948

Gnomad4 FIN exome

AF:

0.0611

Gnomad4 NFE exome

AF:

0.0403

Gnomad4 OTH exome

AF:

0.0532

GnomAD4 genome

AF:

0.0826

AC:

12565

AN:

152074

Hom.:

758

Cov.:

AF XY:

0.0836

AC XY:

6218

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.172

Gnomad4 AMR

AF:

0.0566

Gnomad4 ASJ

AF:

0.0611

Gnomad4 EAS

AF:

0.0614

Gnomad4 SAS

AF:

0.0938

Gnomad4 FIN

AF:

0.0626

Gnomad4 NFE

AF:

0.0403

Gnomad4 OTH

AF:

0.0803

Alfa

AF:

0.0493

Hom.:

510

Bravo

AF:

0.0855

TwinsUK

AF:

0.0369

AC:

137

ALSPAC

AF:

0.0363

AC:

140

ESP6500AA

AF:

0.167

AC:

506

ESP6500EA

AF:

0.0437

AC:

237

ExAC

AF:

0.0669

AC:

7913

Asia WGS

AF:

0.0760

AC:

266

AN:

3478

EpiCase

AF:

0.0441

EpiControl

AF:

0.0449

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.017

T;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.073

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.67

N;.

REVEL

Benign

0.080

Sift

Uncertain

0.0050

D;.

Sift4G

Uncertain

0.016

D;.

Polyphen

0.90

P;P

Vest4

0.099

MPC

0.32

ClinPred

0.017

GERP RS

3.5

Varity_R

0.026

gMVP

0.43

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over