NM_005514.8:c.165C>T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7
The NM_005514.8(HLA-B):c.165C>T(p.Thr55Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 7)
Exomes 𝑓: 0.0000019 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HLA-B
NM_005514.8 synonymous
NM_005514.8 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.0770
Publications
17 publications found
Genes affected
HLA-B (HGNC:4932): (major histocompatibility complex, class I, B) HLA-B belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exon 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-B alleles have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP7
Synonymous conserved (PhyloP=-0.077 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_005514.8. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HLA-B | NM_005514.8 | MANE Select | c.165C>T | p.Thr55Thr | synonymous | Exon 2 of 8 | NP_005505.2 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| HLA-B | ENST00000412585.7 | TSL:6 MANE Select | c.165C>T | p.Thr55Thr | synonymous | Exon 2 of 8 | ENSP00000399168.2 | ||
| HLA-B | ENST00000696559.1 | c.165C>T | p.Thr55Thr | synonymous | Exon 5 of 11 | ENSP00000512717.1 | |||
| HLA-B | ENST00000696560.1 | c.165C>T | p.Thr55Thr | synonymous | Exon 4 of 10 | ENSP00000512718.1 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 57790Hom.: 0 Cov.: 7
GnomAD3 genomes
AF:
AC:
0
AN:
57790
Hom.:
Cov.:
7
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: 0.00000192 AC: 2AN: 1042330Hom.: 0 Cov.: 24 AF XY: 0.00000385 AC XY: 2AN XY: 518990 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:
2
AN:
1042330
Hom.:
Cov.:
24
AF XY:
AC XY:
2
AN XY:
518990
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:
22034
American (AMR)
AF:
AC:
0
AN:
32164
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
20704
East Asian (EAS)
AF:
AC:
0
AN:
25678
South Asian (SAS)
AF:
AC:
1
AN:
57020
European-Finnish (FIN)
AF:
AC:
1
AN:
34066
Middle Eastern (MID)
AF:
AC:
0
AN:
2892
European-Non Finnish (NFE)
AF:
AC:
0
AN:
804376
Other (OTH)
AF:
AC:
0
AN:
43396
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
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>80
Age
GnomAD4 genome 0.00 AC: 0AN: 57790Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0AN XY: 26948
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
57790
Hom.:
Cov.:
7
AF XY:
AC XY:
0
AN XY:
26948
African (AFR)
AF:
AC:
0
AN:
14492
American (AMR)
AF:
AC:
0
AN:
5470
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
1878
East Asian (EAS)
AF:
AC:
0
AN:
1262
South Asian (SAS)
AF:
AC:
0
AN:
1074
European-Finnish (FIN)
AF:
AC:
0
AN:
3792
Middle Eastern (MID)
AF:
AC:
0
AN:
122
European-Non Finnish (NFE)
AF:
AC:
0
AN:
28742
Other (OTH)
AF:
AC:
0
AN:
656
ClinVar
Not reported inComputational 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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