6-32522079-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002125.4(HLA-DRB5):ā€‹c.196G>Cā€‹(p.Asp66His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. D66N) has been classified as Likely benign.

Frequency

Genomes: š‘“ 0.0 ( 0 hom., cov: 13)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

HLA-DRB5
NM_002125.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.46
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.057871282).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HLA-DRB5NM_002125.4 linkc.196G>C p.Asp66His missense_variant 2/6 ENST00000374975.4 NP_002116.2 Q30154A0A2Z4LKS3
HLA-DRB5XM_011514562.3 linkc.196G>C p.Asp66His missense_variant 2/6 XP_011512864.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HLA-DRB5ENST00000374975.4 linkc.196G>C p.Asp66His missense_variant 2/66 NM_002125.4 ENSP00000364114.3 Q30154

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
94930
Hom.:
0
Cov.:
13
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1251064
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
625924
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
94930
Hom.:
0
Cov.:
13
AF XY:
0.00
AC XY:
0
AN XY:
45222
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
0.0010
DANN
Benign
0.32
DEOGEN2
Benign
0.0071
T
Eigen
Benign
-2.7
Eigen_PC
Benign
-2.8
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.10
T
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.058
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.76
N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
2.1
N
REVEL
Benign
0.13
Sift
Benign
0.17
T
Sift4G
Benign
0.12
T
Polyphen
0.59
P
Vest4
0.13
MutPred
0.10
Gain of sheet (P = 0.0827);
MVP
0.055
MPC
0.018
ClinPred
0.83
D
GERP RS
-9.6
Varity_R
0.29
gMVP
0.33

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.

Other links and lift over

dbSNP: rs707956; hg19: chr6-32489856; API