dbSNP rs202054400: HLA-DRB5:p.Arg134Ser (chr6-32519620-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002125.4(HLA-DRB5):c.402G>C(p.Arg134Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R134R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 7)

Exomes 𝑓: 0.0000013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HLA-DRB5
NM_002125.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.166

Publications

0 publications found

Variant links:

Genes affected

HLA-DRB5 (HGNC:4953): (major histocompatibility complex, class II, DR beta 5) HLA-DRB5 belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DRA) and a beta (DRB) 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. 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 DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. There are multiple pseudogenes of this gene. [provided by RefSeq, Feb 2020]

HLA-DRB5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14377668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DRB5	NM_002125.4 link	c.402G>C	p.Arg134Ser	missense_variant	Exon 3 of 6	ENST00000374975.4	NP_002116.2	Q30154A0A2Z4LKS3
HLA-DRB5	XM_011514562.3 link	c.402G>C	p.Arg134Ser	missense_variant	Exon 3 of 6		XP_011512864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DRB5	ENST00000374975.4 link	c.402G>C	p.Arg134Ser	missense_variant	Exon 3 of 6	6	NM_002125.4	ENSP00000364114.3		Q30154
HLA-DRB5	ENST00000714490.1 link	c.371-59G>C		intron_variant	Intron 2 of 5			ENSP00000519744.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000167

AC:

AN:

119482

AF XY:

0.0000306

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000133

AC:

AN:

750406

Hom.:

Cov.:

AF XY:

0.00000261

AC XY:

AN XY:

383488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

14866

American (AMR)

AF:

0.00

AC:

AN:

28654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14268

East Asian (EAS)

AF:

0.00

AC:

AN:

28406

South Asian (SAS)

AF:

0.0000189

AC:

AN:

52782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33654

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2838

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

541278

Other (OTH)

AF:

0.00

AC:

AN:

33660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.925

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000184

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.79

M_CAP

Benign

0.0037

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.57

PhyloP100

0.17

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.1

REVEL

Benign

0.084

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.041

Polyphen

0.0

Vest4

0.18

MutPred

0.61

Loss of sheet (P = 0.0357);

MVP

0.25

MPC

1.6

ClinPred

0.23

GERP RS

3.8

Varity_R

0.64

gMVP

0.30

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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rs202054400

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over