Variant 6-32584318-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_002124.4(HLA-DRB1):c.161G>A(p.Arg54Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 984,110 control chromosomes in the GnomAD database, including 358 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.017 ( 0 hom., cov: 15)

Exomes 𝑓: 0.027 ( 358 hom. )

Consequence

HLA-DRB1
NM_002124.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.846

Variant links:

Genes affected

HLA-DRB1 (HGNC:4948): (major histocompatibility complex, class II, DR beta 1) HLA-DRB1 belongs to the HLA class II beta chain paralogs. The class II molecule is a heterodimer consisting of an alpha (DRA) and a beta chain (DRB), 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. The beta chain is approximately 26-28 kDa. It is encoded by 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 DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Hundreds of DRB1 alleles have been described and some alleles have increased frequencies associated with certain diseases or conditions. For example, DRB1*1302 has been related to acute and chronic hepatitis B virus persistence. There are multiple pseudogenes of this gene. [provided by RefSeq, Jul 2020]

HLA-DRB1 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=0.0068374574).

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DRB1	NM_002124.4 link	c.161G>A	p.Arg54Gln	missense_variant	2/6	ENST00000360004.6	NP_002115.2	P01911D7RIH8A0A224MM52X5DNQ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DRB1	ENST00000360004.6 link	c.161G>A	p.Arg54Gln	missense_variant	2/6	6	NM_002124.4	ENSP00000353099.5		P01911

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

1509

AN:

87000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.0584

Gnomad AMR

AF:

0.0153

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.00844

Gnomad SAS

AF:

0.0193

Gnomad FIN

AF:

0.00749

Gnomad MID

AF:

0.00505

Gnomad NFE

AF:

0.0235

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.000191

AC:

AN:

151644

Hom.:

AF XY:

0.000204

AC XY:

AN XY:

83406

show subpopulations

Gnomad AFR exome

AF:

0.000106

Gnomad AMR exome

AF:

0.000201

Gnomad ASJ exome

AF:

0.000321

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000286

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000173

Gnomad OTH exome

AF:

0.00113

GnomAD4 exome

AF:

0.0271

AC:

24294

AN:

897028

Hom.:

358

Cov.:

AF XY:

0.0281

AC XY:

12765

AN XY:

454044

show subpopulations

Gnomad4 AFR exome

AF:

0.0170

Gnomad4 AMR exome

AF:

0.0276

Gnomad4 ASJ exome

AF:

0.0312

Gnomad4 EAS exome

AF:

0.00612

Gnomad4 SAS exome

AF:

0.0297

Gnomad4 FIN exome

AF:

0.0118

Gnomad4 NFE exome

AF:

0.0285

Gnomad4 OTH exome

AF:

0.0247

GnomAD4 genome

AF:

0.0173

AC:

1509

AN:

87082

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

703

AN XY:

42568

show subpopulations

Gnomad4 AFR

AF:

0.0115

Gnomad4 AMR

AF:

0.0153

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.00850

Gnomad4 SAS

AF:

0.0183

Gnomad4 FIN

AF:

0.00749

Gnomad4 NFE

AF:

0.0235

Gnomad4 OTH

AF:

0.0169

Alfa

AF:

0.117

Hom.:

294

ExAC

AF:

0.000355

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0068

MetaSVM

Benign

-0.92

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.13

Sift

Uncertain

0.023

Sift4G

Benign

0.063

Polyphen

0.016

Vest4

0.31

MVP

0.17

MPC

0.96

ClinPred

0.026

GERP RS

1.7

Varity_R

0.48

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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