chr6-32521939-G-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_002125.4(HLA-DRB5):c.336C>T(p.Tyr112Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000153 in 130,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000015 ( 0 hom., cov: 21)
Exomes 𝑓: 0.0000036 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HLA-DRB5
NM_002125.4 synonymous
NM_002125.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0840
Publications
0 publications found
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]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 6-32521939-G-A is Benign according to our data. Variant chr6-32521939-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656454.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.084 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| HLA-DRB5 | NM_002125.4 | c.336C>T | p.Tyr112Tyr | synonymous_variant | Exon 2 of 6 | ENST00000374975.4 | NP_002116.2 | |
| HLA-DRB5 | XM_011514562.3 | c.336C>T | p.Tyr112Tyr | synonymous_variant | Exon 2 of 6 | XP_011512864.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000153 AC: 2AN: 130398Hom.: 0 Cov.: 21 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
130398
Hom.:
Cov.:
21
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000356 AC: 5AN: 1405444Hom.: 0 Cov.: 39 AF XY: 0.00000285 AC XY: 2AN XY: 700850 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
5
AN:
1405444
Hom.:
Cov.:
39
AF XY:
AC XY:
2
AN XY:
700850
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
32112
American (AMR)
AF:
AC:
0
AN:
43110
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24042
East Asian (EAS)
AF:
AC:
1
AN:
38688
South Asian (SAS)
AF:
AC:
0
AN:
84524
European-Finnish (FIN)
AF:
AC:
0
AN:
51936
Middle Eastern (MID)
AF:
AC:
0
AN:
5484
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1067782
Other (OTH)
AF:
AC:
1
AN:
57766
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000051), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.305
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000153 AC: 2AN: 130502Hom.: 0 Cov.: 21 AF XY: 0.0000157 AC XY: 1AN XY: 63564 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
130502
Hom.:
Cov.:
21
AF XY:
AC XY:
1
AN XY:
63564
show subpopulations
African (AFR)
AF:
AC:
1
AN:
36134
American (AMR)
AF:
AC:
1
AN:
12262
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2668
East Asian (EAS)
AF:
AC:
0
AN:
4402
South Asian (SAS)
AF:
AC:
0
AN:
4050
European-Finnish (FIN)
AF:
AC:
0
AN:
9082
Middle Eastern (MID)
AF:
AC:
0
AN:
258
European-Non Finnish (NFE)
AF:
AC:
0
AN:
59206
Other (OTH)
AF:
AC:
0
AN:
1734
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Aug 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
HLA-DRB5: BP4, BP7 -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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