rs1071652

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005514.8(HLA-B):​c.362G>T​(p.Ser121Ile) variant causes a missense 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. 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 0.00042 ( 0 hom., cov: 4)
Exomes 𝑓: 0.0032 ( 26 hom. )

Consequence

HLA-B
NM_005514.8 missense

Scores

16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.73
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 Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HLA-BNM_005514.8 linkuse as main transcriptc.362G>T p.Ser121Ile 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.362G>T p.Ser121Ile missense_variant 3/8 NM_005514.8 P1

Frequencies

GnomAD3 genomes
AF:
0.000425
AC:
19
AN:
44734
Hom.:
0
Cov.:
4
show subpopulations
Gnomad AFR
AF:
0.00104
Gnomad AMI
AF:
0.00495
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000215
Gnomad OTH
AF:
0.00219
GnomAD3 exomes
AF:
0.0198
AC:
3623
AN:
182648
Hom.:
260
AF XY:
0.0203
AC XY:
2007
AN XY:
98730
show subpopulations
Gnomad AFR exome
AF:
0.0446
Gnomad AMR exome
AF:
0.0110
Gnomad ASJ exome
AF:
0.0363
Gnomad EAS exome
AF:
0.00165
Gnomad SAS exome
AF:
0.0396
Gnomad FIN exome
AF:
0.00643
Gnomad NFE exome
AF:
0.0189
Gnomad OTH exome
AF:
0.0233
GnomAD4 exome
AF:
0.00320
AC:
2789
AN:
871158
Hom.:
26
Cov.:
14
AF XY:
0.00352
AC XY:
1522
AN XY:
432650
show subpopulations
Gnomad4 AFR exome
AF:
0.00571
Gnomad4 AMR exome
AF:
0.00347
Gnomad4 ASJ exome
AF:
0.00936
Gnomad4 EAS exome
AF:
0.000428
Gnomad4 SAS exome
AF:
0.00952
Gnomad4 FIN exome
AF:
0.000824
Gnomad4 NFE exome
AF:
0.00269
Gnomad4 OTH exome
AF:
0.00438
GnomAD4 genome
AF:
0.000425
AC:
19
AN:
44752
Hom.:
0
Cov.:
4
AF XY:
0.000426
AC XY:
9
AN XY:
21134
show subpopulations
Gnomad4 AFR
AF:
0.00104
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000215
Gnomad4 OTH
AF:
0.00216
Alfa
AF:
0.0150
Hom.:
47
ExAC
AF:
0.0288
AC:
3246

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
12
DANN
Benign
0.84
DEOGEN2
Benign
0.022
T;.;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.048
N
LIST_S2
Benign
0.0037
T;T;T
MetaRNN
Benign
0.0053
T;T;T
MetaSVM
Benign
-0.87
T
MutationTaster
Benign
1.0
N
PROVEAN
Benign
-1.2
N;.;N
REVEL
Benign
0.24
Sift
Benign
0.17
T;.;D
Sift4G
Benign
0.26
T;.;T
Polyphen
0.78
P;.;.
Vest4
0.049
MPC
0.73
ClinPred
0.021
T
GERP RS
-6.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.23
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.32
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.32
Position offset: 1

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: rs1071652; hg19: chr6-31324201; API