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GeneBe

rs8084

Positions:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_019111.5(HLA-DRA):ā€‹c.402A>Cā€‹(p.Ile134=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,611,822 control chromosomes in the GnomAD database, including 277,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

Frequency

Genomes: š‘“ 0.59 ( 26922 hom., cov: 30)
Exomes š‘“: 0.58 ( 250974 hom. )

Consequence

HLA-DRA
NM_019111.5 synonymous

Scores

7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.39
Variant links:
Genes affected
HLA-DRA (HGNC:4947): (major histocompatibility complex, class II, DR alpha) HLA-DRA is one of the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha and a beta chain, both anchored in the membrane. This molecule is expressed on the surface of various antigen presenting cells such as B lymphocytes, dendritic cells, and monocytes/macrophages, and plays a central role in the immune system and response by presenting peptides derived from extracellular proteins, in particular, pathogen-derived peptides to T cells. The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5. [provided by RefSeq, Aug 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_addAF=-0.911607).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-32443258-A-C is Benign according to our data. Variant chr6-32443258-A-C is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.39 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HLA-DRANM_019111.5 linkuse as main transcriptc.402A>C p.Ile134= synonymous_variant 3/5 ENST00000395388.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HLA-DRAENST00000395388.7 linkuse as main transcriptc.402A>C p.Ile134= synonymous_variant 3/5 NM_019111.5 P1
HLA-DRAENST00000374982.5 linkuse as main transcriptc.329-2A>C splice_acceptor_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.592
AC:
89777
AN:
151748
Hom.:
26903
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.591
Gnomad AMI
AF:
0.610
Gnomad AMR
AF:
0.658
Gnomad ASJ
AF:
0.730
Gnomad EAS
AF:
0.699
Gnomad SAS
AF:
0.684
Gnomad FIN
AF:
0.505
Gnomad MID
AF:
0.715
Gnomad NFE
AF:
0.567
Gnomad OTH
AF:
0.628
GnomAD3 exomes
AF:
0.611
AC:
150710
AN:
246556
Hom.:
47059
AF XY:
0.618
AC XY:
83027
AN XY:
134378
show subpopulations
Gnomad AFR exome
AF:
0.589
Gnomad AMR exome
AF:
0.614
Gnomad ASJ exome
AF:
0.725
Gnomad EAS exome
AF:
0.720
Gnomad SAS exome
AF:
0.717
Gnomad FIN exome
AF:
0.510
Gnomad NFE exome
AF:
0.575
Gnomad OTH exome
AF:
0.618
GnomAD4 exome
AF:
0.582
AC:
850280
AN:
1459956
Hom.:
250974
Cov.:
44
AF XY:
0.588
AC XY:
426854
AN XY:
726322
show subpopulations
Gnomad4 AFR exome
AF:
0.586
Gnomad4 AMR exome
AF:
0.623
Gnomad4 ASJ exome
AF:
0.719
Gnomad4 EAS exome
AF:
0.656
Gnomad4 SAS exome
AF:
0.717
Gnomad4 FIN exome
AF:
0.508
Gnomad4 NFE exome
AF:
0.567
Gnomad4 OTH exome
AF:
0.589
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.592
AC:
89839
AN:
151866
Hom.:
26922
Cov.:
30
AF XY:
0.593
AC XY:
44034
AN XY:
74198
show subpopulations
Gnomad4 AFR
AF:
0.591
Gnomad4 AMR
AF:
0.658
Gnomad4 ASJ
AF:
0.730
Gnomad4 EAS
AF:
0.698
Gnomad4 SAS
AF:
0.685
Gnomad4 FIN
AF:
0.505
Gnomad4 NFE
AF:
0.567
Gnomad4 OTH
AF:
0.630
Alfa
AF:
0.581
Hom.:
36812
Bravo
AF:
0.604
TwinsUK
AF:
0.566
AC:
2100
ALSPAC
AF:
0.585
AC:
2253
ESP6500AA
AF:
0.572
AC:
1728
ESP6500EA
AF:
0.569
AC:
3084
ExAC
?
    Exome Aggregation Consortium database
AF:
0.607
AC:
71560
Asia WGS
AF:
0.673
AC:
2345
AN:
3478
EpiCase
AF:
0.607
EpiControl
AF:
0.621

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.91
T
BayesDel_noAF
Benign
-0.94
CADD
Benign
2.4
DANN
Benign
0.45
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0069
N
MutationTaster
Benign
0.00017
P;P
GERP RS
-9.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs8084; hg19: chr6-32411035; COSMIC: COSV66622864; API