6-31356424-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005514.8(HLA-B):​c.362G>C​(p.Ser121Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 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. S121R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.011 ( 36 hom., cov: 4)
Exomes 𝑓: 0.027 ( 1487 hom. )
Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 missense

Scores

16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.73

Publications

27 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0037901402).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HLA-BNM_005514.8 linkc.362G>C p.Ser121Thr missense_variant Exon 3 of 8 ENST00000412585.7 NP_005505.2 P01889E5FQ95

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HLA-BENST00000412585.7 linkc.362G>C p.Ser121Thr missense_variant Exon 3 of 8 6 NM_005514.8 ENSP00000399168.2 P01889

Frequencies

GnomAD3 genomes
AF:
0.0113
AC:
498
AN:
44240
Hom.:
36
Cov.:
4
show subpopulations
Gnomad AFR
AF:
0.00365
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0141
Gnomad ASJ
AF:
0.0244
Gnomad EAS
AF:
0.0452
Gnomad SAS
AF:
0.0400
Gnomad FIN
AF:
0.00960
Gnomad MID
AF:
0.0333
Gnomad NFE
AF:
0.0118
Gnomad OTH
AF:
0.0176
GnomAD2 exomes
AF:
0.0664
AC:
12126
AN:
182648
AF XY:
0.0724
show subpopulations
Gnomad AFR exome
AF:
0.0317
Gnomad AMR exome
AF:
0.0557
Gnomad ASJ exome
AF:
0.0512
Gnomad EAS exome
AF:
0.101
Gnomad FIN exome
AF:
0.0321
Gnomad NFE exome
AF:
0.0385
Gnomad OTH exome
AF:
0.0722
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0272
AC:
23382
AN:
860730
Hom.:
1487
Cov.:
14
AF XY:
0.0327
AC XY:
13956
AN XY:
426808
show subpopulations
African (AFR)
AF:
0.00920
AC:
174
AN:
18904
American (AMR)
AF:
0.0270
AC:
694
AN:
25728
Ashkenazi Jewish (ASJ)
AF:
0.0473
AC:
473
AN:
10000
East Asian (EAS)
AF:
0.140
AC:
3048
AN:
21738
South Asian (SAS)
AF:
0.185
AC:
8943
AN:
48460
European-Finnish (FIN)
AF:
0.0241
AC:
605
AN:
25076
Middle Eastern (MID)
AF:
0.0701
AC:
115
AN:
1640
European-Non Finnish (NFE)
AF:
0.0122
AC:
8246
AN:
676134
Other (OTH)
AF:
0.0328
AC:
1084
AN:
33050
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
463
926
1388
1851
2314
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
198
396
594
792
990
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0113
AC:
500
AN:
44258
Hom.:
36
Cov.:
4
AF XY:
0.00976
AC XY:
204
AN XY:
20898
show subpopulations
African (AFR)
AF:
0.00364
AC:
42
AN:
11524
American (AMR)
AF:
0.0141
AC:
48
AN:
3404
Ashkenazi Jewish (ASJ)
AF:
0.0244
AC:
10
AN:
410
East Asian (EAS)
AF:
0.0448
AC:
64
AN:
1428
South Asian (SAS)
AF:
0.0403
AC:
22
AN:
546
European-Finnish (FIN)
AF:
0.00960
AC:
31
AN:
3228
Middle Eastern (MID)
AF:
0.0333
AC:
1
AN:
30
European-Non Finnish (NFE)
AF:
0.0118
AC:
271
AN:
23024
Other (OTH)
AF:
0.0238
AC:
11
AN:
462
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.417
Heterozygous variant carriers
0
23
46
69
92
115
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0507
Hom.:
47
ExAC
AF:
0.101
AC:
11351

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.68
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
2.0
DANN
Benign
0.43
DEOGEN2
Benign
0.017
T;.;T
Eigen
Benign
-1.9
Eigen_PC
Benign
-2.1
FATHMM_MKL
Benign
0.056
N
LIST_S2
Benign
0.0024
T;T;T
MetaRNN
Benign
0.0038
T;T;T
MetaSVM
Benign
-0.96
T
PhyloP100
-2.7
PROVEAN
Benign
0.28
N;.;N
REVEL
Benign
0.14
Sift
Benign
0.60
T;.;T
Sift4G
Benign
0.64
T;.;T
Polyphen
0.0
B;.;.
Vest4
0.048
MPC
0.20
ClinPred
0.00066
T
GERP RS
-6.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.19
gMVP
0.090
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs1071652; hg19: chr6-31324201; COSMIC: COSV69520609; COSMIC: COSV69520609; API