rs2308466

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005514.8(HLA-B):​c.560A>T​(p.Glu187Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/18 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. E187L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.11 ( 460 hom., cov: 4)
Exomes 𝑓: 0.23 ( 16763 hom. )
Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 missense

Scores

16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -8.96
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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0052467883).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HLA-BNM_005514.8 linkuse as main transcriptc.560A>T p.Glu187Val missense_variant 3/8 ENST00000412585.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HLA-BENST00000412585.7 linkuse as main transcriptc.560A>T p.Glu187Val missense_variant 3/8 NM_005514.8 P1

Frequencies

GnomAD3 genomes
AF:
0.111
AC:
3500
AN:
31468
Hom.:
460
Cov.:
4
show subpopulations
Gnomad AFR
AF:
0.176
Gnomad AMI
AF:
0.152
Gnomad AMR
AF:
0.166
Gnomad ASJ
AF:
0.139
Gnomad EAS
AF:
0.151
Gnomad SAS
AF:
0.183
Gnomad FIN
AF:
0.0436
Gnomad MID
AF:
0.459
Gnomad NFE
AF:
0.0778
Gnomad OTH
AF:
0.219
GnomAD3 exomes
AF:
0.381
AC:
64927
AN:
170240
Hom.:
6716
AF XY:
0.381
AC XY:
35450
AN XY:
92970
show subpopulations
Gnomad AFR exome
AF:
0.432
Gnomad AMR exome
AF:
0.435
Gnomad ASJ exome
AF:
0.321
Gnomad EAS exome
AF:
0.480
Gnomad SAS exome
AF:
0.404
Gnomad FIN exome
AF:
0.342
Gnomad NFE exome
AF:
0.348
Gnomad OTH exome
AF:
0.384
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.231
AC:
209131
AN:
905958
Hom.:
16763
Cov.:
17
AF XY:
0.232
AC XY:
106037
AN XY:
456104
show subpopulations
Gnomad4 AFR exome
AF:
0.392
Gnomad4 AMR exome
AF:
0.329
Gnomad4 ASJ exome
AF:
0.323
Gnomad4 EAS exome
AF:
0.300
Gnomad4 SAS exome
AF:
0.297
Gnomad4 FIN exome
AF:
0.169
Gnomad4 NFE exome
AF:
0.211
Gnomad4 OTH exome
AF:
0.257
GnomAD4 genome
AF:
0.111
AC:
3501
AN:
31466
Hom.:
460
Cov.:
4
AF XY:
0.108
AC XY:
1594
AN XY:
14806
show subpopulations
Gnomad4 AFR
AF:
0.177
Gnomad4 AMR
AF:
0.168
Gnomad4 ASJ
AF:
0.139
Gnomad4 EAS
AF:
0.152
Gnomad4 SAS
AF:
0.179
Gnomad4 FIN
AF:
0.0436
Gnomad4 NFE
AF:
0.0777
Gnomad4 OTH
AF:
0.216
Alfa
AF:
0.307
Hom.:
515
ESP6500AA
AF:
0.542
AC:
2317
ESP6500EA
AF:
0.464
AC:
3870
ExAC
AF:
0.381
AC:
45558

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.60
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
0.076
DANN
Benign
0.47
DEOGEN2
Benign
0.026
T;.;T
Eigen
Benign
-2.3
Eigen_PC
Benign
-2.5
FATHMM_MKL
Benign
0.017
N
LIST_S2
Benign
0.0019
T;T;T
MetaRNN
Benign
0.0052
T;T;T
MetaSVM
Benign
-0.92
T
MutationTaster
Benign
1.0
P
PROVEAN
Benign
-1.9
N;.;N
REVEL
Benign
0.24
Sift
Benign
0.055
T;.;T
Sift4G
Benign
0.19
T;.;T
Polyphen
0.019
B;.;.
Vest4
0.042
MPC
0.27
ClinPred
0.028
T
GERP RS
-6.4
Varity_R
0.57
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs2308466; hg19: chr6-31324003; COSMIC: COSV69520675; COSMIC: COSV69520675; API