HLA-B p.Glu100Val

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005514.8(HLA-B):c.299A>T(p.Glu100Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.00073 ( 2 hom., cov: 7)

Exomes 𝑓: 0.0079 ( 157 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.33

Publications

21 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:

ENSG00000271581 (HGNC:):

ENSG00000271581 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_005514.8, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026462972).

BS2

High AC in GnomAd4 at 42 AD gene.

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.299A>T	p.Glu100Val	missense	Exon 2 of 8	NP_005505.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HLA-B	ENST00000412585.7	TSL:6 MANE Select	c.299A>T	p.Glu100Val	missense	Exon 2 of 8	ENSP00000399168.2	P01889
HLA-B	ENST00000696559.1		c.299A>T	p.Glu100Val	missense	Exon 5 of 11	ENSP00000512717.1	P01889
HLA-B	ENST00000696560.1		c.299A>T	p.Glu100Val	missense	Exon 4 of 10	ENSP00000512718.1	P01889

Frequencies

GnomAD3 genomes

AF:

0.000732

AC:

AN:

57406

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.000635

Gnomad EAS

AF:

0.00527

Gnomad SAS

AF:

0.00107

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0122

Gnomad NFE

AF:

0.000534

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.0133

AC:

2756

AN:

207848

AF XY:

0.0123

show subpopulations

Gnomad AFR exome

AF:

0.00359

Gnomad AMR exome

AF:

0.00914

Gnomad ASJ exome

AF:

0.00399

Gnomad EAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.00195

Gnomad NFE exome

AF:

0.00619

Gnomad OTH exome

AF:

0.0120

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00792

AC:

7851

AN:

991846

Hom.:

157

Cov.:

AF XY:

0.00806

AC XY:

3967

AN XY:

492354

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00926

AC:

177

AN:

19122

American (AMR)

AF:

0.00837

AC:

252

AN:

30100

Ashkenazi Jewish (ASJ)

AF:

0.00454

AC:

AN:

18048

East Asian (EAS)

AF:

0.0296

AC:

670

AN:

22600

South Asian (SAS)

AF:

0.0119

AC:

632

AN:

53190

European-Finnish (FIN)

AF:

0.00257

AC:

AN:

33082

Middle Eastern (MID)

AF:

0.0143

AC:

AN:

3010

European-Non Finnish (NFE)

AF:

0.00724

AC:

5594

AN:

772494

Other (OTH)

AF:

0.00786

AC:

316

AN:

40200

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.318

Heterozygous variant carriers

630

1259

1889

2518

3148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

268

536

804

1072

1340

<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

AF:

0.000731

AC:

AN:

57464

Hom.:

Cov.:

AF XY:

0.000906

AC XY:

AN XY:

27588

show subpopulations

African (AFR)

AF:

0.000601

AC:

AN:

14968

American (AMR)

AF:

0.000784

AC:

AN:

5100

Ashkenazi Jewish (ASJ)

AF:

0.000635

AC:

AN:

1574

East Asian (EAS)

AF:

0.00529

AC:

AN:

1512

South Asian (SAS)

AF:

0.00106

AC:

AN:

940

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4162

Middle Eastern (MID)

AF:

0.0132

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000534

AC:

AN:

28088

Other (OTH)

AF:

0.00419

AC:

AN:

716

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00763

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.5

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.016

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.010

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

PhyloP100

-4.3

PROVEAN

Benign

2.9

REVEL

Uncertain

0.32

Sift

Benign

0.29

Sift4G

Benign

1.0

PromoterAI

-0.0033

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.31

gMVP

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over