dbSNP rs4740: EBI3:p.Val201Ile (chr19-4236999-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005755.3(EBI3):c.601G>A(p.Val201Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,580,534 control chromosomes in the GnomAD database, including 83,983 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.39 ( 12763 hom., cov: 31)

Exomes 𝑓: 0.31 ( 71220 hom. )

Consequence

EBI3
NM_005755.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

Publications

69 publications found

Variant links:

Genes affected

EBI3 (HGNC:3129): (Epstein-Barr virus induced 3) This gene was identified by its induced expression in B lymphocytes in response Epstein-Barr virus infection. It encodes a secreted glycoprotein belonging to the hematopoietin receptor family, and heterodimerizes with a 28 kDa protein to form interleukin 27 (IL-27). IL-27 regulates T cell and inflammatory responses, in part by activating the Jak/STAT pathway of CD4+ T cells. [provided by RefSeq, Sep 2008]

EBI3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.1727625E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBI3	NM_005755.3 link	c.601G>A	p.Val201Ile	missense_variant	Exon 5 of 5	ENST00000221847.6	NP_005746.2	Q14213

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBI3	ENST00000221847.6 link	c.601G>A	p.Val201Ile	missense_variant	Exon 5 of 5	1	NM_005755.3	ENSP00000221847.4		Q14213

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58682

AN:

151788

Hom.:

12733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.586

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.450

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.290

Gnomad OTH

AF:

0.378

GnomAD2 exomes

AF:

0.337

AC:

77651

AN:

230400

AF XY:

0.339

show subpopulations

Gnomad AFR exome

AF:

0.591

Gnomad AMR exome

AF:

0.268

Gnomad ASJ exome

AF:

0.322

Gnomad EAS exome

AF:

0.457

Gnomad FIN exome

AF:

0.289

Gnomad NFE exome

AF:

0.287

Gnomad OTH exome

AF:

0.316

GnomAD4 exome

AF:

0.308

AC:

440182

AN:

1428630

Hom.:

71220

Cov.:

AF XY:

0.312

AC XY:

221077

AN XY:

708398

show subpopulations

African (AFR)

AF:

0.598

AC:

18798

AN:

31452

American (AMR)

AF:

0.278

AC:

11791

AN:

42438

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

8287

AN:

24986

East Asian (EAS)

AF:

0.414

AC:

15299

AN:

36950

South Asian (SAS)

AF:

0.449

AC:

37421

AN:

83376

European-Finnish (FIN)

AF:

0.298

AC:

15714

AN:

52688

Middle Eastern (MID)

AF:

0.373

AC:

2105

AN:

5644

European-Non Finnish (NFE)

AF:

0.285

AC:

311069

AN:

1092332

Other (OTH)

AF:

0.335

AC:

19698

AN:

58764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

16186

32372

48558

64744

80930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10714

21428

32142

42856

53570

<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:

0.387

AC:

58751

AN:

151904

Hom.:

12763

Cov.:

AF XY:

0.385

AC XY:

28614

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.585

AC:

24230

AN:

41386

American (AMR)

AF:

0.318

AC:

4851

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

1142

AN:

3472

East Asian (EAS)

AF:

0.451

AC:

2328

AN:

5166

South Asian (SAS)

AF:

0.463

AC:

2231

AN:

4818

European-Finnish (FIN)

AF:

0.286

AC:

3016

AN:

10562

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.290

AC:

19690

AN:

67940

Other (OTH)

AF:

0.379

AC:

799

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1651

3302

4953

6604

8255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.323

Hom.:

38287

Bravo

AF:

0.395

TwinsUK

AF:

0.289

AC:

1070

ALSPAC

AF:

0.289

AC:

1115

ESP6500AA

AF:

0.584

AC:

2572

ESP6500EA

AF:

0.286

AC:

2456

ExAC

AF:

0.354

AC:

42907

Asia WGS

AF:

0.467

AC:

1623

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.0030

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.12

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.59

MetaRNN

Benign

0.000022

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.28

PhyloP100

-1.5

PrimateAI

Benign

0.31

PROVEAN

Benign

0.27

REVEL

Benign

0.067

Sift

Benign

0.99

Sift4G

Benign

0.97

Polyphen

0.060

Vest4

0.074

MPC

0.087

ClinPred

0.0063

GERP RS

-8.9

Varity_R

0.035

gMVP

0.12

Mutation Taster

=98/2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over