Genetic Variant HLA-B:p.Glu187Gly (chr6-31356226-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_005514.8(HLA-B):c.560A>G(p.Glu187Gly) 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.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 4)

Exomes 𝑓: 0.000085 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -8.96

Publications

34 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]

HLA-B links:

ENSG00000298396 (HGNC:):

ENSG00000298396 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-B	NM_005514.8 link	c.560A>G	p.Glu187Gly	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-B	ENST00000412585.7 link	c.560A>G	p.Glu187Gly	missense_variant	Exon 3 of 8	6	NM_005514.8	ENSP00000399168.2		P01889

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

37264

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000211

AC:

AN:

170240

AF XY:

0.000183

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000424

Gnomad ASJ exome

AF:

0.000511

Gnomad EAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.000737

Gnomad NFE exome

AF:

0.000201

Gnomad OTH exome

AF:

0.000230

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000854

AC:

AN:

1018814

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

511782

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25058

American (AMR)

AF:

0.0000309

AC:

AN:

32352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16884

East Asian (EAS)

AF:

0.00

AC:

AN:

28644

South Asian (SAS)

AF:

0.00105

AC:

AN:

71560

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3040

European-Non Finnish (NFE)

AF:

0.00000261

AC:

AN:

767336

Other (OTH)

AF:

0.000217

AC:

AN:

41486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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: AC0

AF:

0.00

AC:

AN:

37264

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

17460

African (AFR)

AF:

0.00

AC:

AN:

7560

American (AMR)

AF:

0.00

AC:

AN:

3030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

406

East Asian (EAS)

AF:

0.00

AC:

AN:

1536

South Asian (SAS)

AF:

0.00

AC:

AN:

930

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

20458

Other (OTH)

AF:

0.00

AC:

AN:

430

Alfa

AF:

0.00

Hom.:

515

ExAC

AF:

0.000401

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.1

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.018

T;.;T

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.0018

T;T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.046

T;T;T

MetaSVM

Benign

-0.89

PhyloP100

-9.0

PROVEAN

Uncertain

-2.7

D;.;N

REVEL

Benign

0.28

Sift

Benign

0.069

T;.;T

Sift4G

Benign

0.26

T;.;T

Polyphen

0.0

B;.;.

Vest4

0.20

MVP

0.030

MPC

0.29

ClinPred

0.11

GERP RS

-6.4

Varity_R

0.60

gMVP

0.30

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.52

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.52

Position offset: 0

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over