HLA-B p.Glu187Gly

Variant names:

• chr6-31356226-T-C
• rs2308466
• NM_005514.8:c.560A>G
• HLA-B p.Glu187Gly

Your query was ambiguous. Multiple possible variants found:

• chr6-31356226-T-C
• chr6-31356225-CT-AC
• chr6-31356225-CT-GC
• chr6-31356225-CT-TC

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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E187K) has been classified as Uncertain significance.

• 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.96
• Publications: 34 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]

ENSG00000298396 (HGNC:):

ACMG classification

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-B	NM_005514.8	MANE Select	c.560A>G	p.Glu187Gly	missense	Exon 3 of 8	NP_005505.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-B	ENST00000412585.7	TSL:6 MANE Select	c.560A>G	p.Glu187Gly	missense	Exon 3 of 8	ENSP00000399168.2	P01889
	HLA-B	ENST00000696559.1		c.560A>G	p.Glu187Gly	missense	Exon 6 of 11	ENSP00000512717.1	P01889
	HLA-B	ENST00000696560.1		c.560A>G	p.Glu187Gly	missense	Exon 5 of 10	ENSP00000512718.1	P01889

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 37264 Hom.: 0 Cov.: 4

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: 36 AN: 170240 AF XY: 0.000183

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: 87 AN: 1018814 Hom.: 0 Cov.: 17 AF XY: 0.000119 AC XY: 61 AN XY: 511782

African (AFR) AF: 0.00 AC: 0 AN: 25058

American (AMR) AF: 0.0000309 AC: 1 AN: 32352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16884

East Asian (EAS) AF: 0.00 AC: 0 AN: 28644

South Asian (SAS) AF: 0.00105 AC: 75 AN: 71560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3040

European-Non Finnish (NFE) AF: 0.00000261 AC: 2 AN: 767336

Other (OTH) AF: 0.000217 AC: 9 AN: 41486

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 37264 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 17460

African (AFR) AF: 0.00 AC: 0 AN: 7560

American (AMR) AF: 0.00 AC: 0 AN: 3030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 406

East Asian (EAS) AF: 0.00 AC: 0 AN: 1536

South Asian (SAS) AF: 0.00 AC: 0 AN: 930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2684

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 76

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 20458

Other (OTH) AF: 0.00 AC: 0 AN: 430

Alfa AF: 0.00 Hom.: 515

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.1
DANN	Benign	0.74
DEOGEN2	Benign	0.018	T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.0018	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.89	T
PhyloP100		-9.0
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.28
Sift	Benign	0.069	T
Sift4G	Benign	0.26	T
Varity_R		0.60
gMVP		0.30
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2308466;

hg19: chr6-31324003;