rs4740

chr19-4236999-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.39 (12763 hom., cov: 31)
  • Exomes 𝑓: 0.31 (71220 hom.)
• Consequence: EBI3 NM_005755.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
EBI3	NM_005755.3	c.601G>A	p.Val201Ile	missense_variant	5/5	ENST00000221847.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EBI3	ENST00000221847.6	c.601G>A	p.Val201Ile	missense_variant	5/5	1	NM_005755.3	P1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58682 AN: 151788 Hom.: 12733 Cov.: 31

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

GnomAD3 exomes AF: 0.337 AC: 77651 AN: 230400 Hom.: 14304 AF XY: 0.339 AC XY: 42422 AN XY: 125134

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 SAS exome AF: 0.448

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.: 34 AF XY: 0.312 AC XY: 221077 AN XY: 708398

Gnomad4 AFR exome AF: 0.598

Gnomad4 AMR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.332

Gnomad4 EAS exome AF: 0.414

Gnomad4 SAS exome AF: 0.449

Gnomad4 FIN exome AF: 0.298

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.335

GnomAD4 genome AF: 0.387 AC: 58751 AN: 151904 Hom.: 12763 Cov.: 31 AF XY: 0.385 AC XY: 28614 AN XY: 74264

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.379

Alfa AF: 0.313 Hom.: 18491

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	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	0.0030
Dann	Benign	0.42
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.000022	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.28	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.067
Sift	Benign	0.99	T
Sift4G	Benign	0.97	T
Polyphen		0.060	B
Vest4		0.074
MPC		0.087
ClinPred		0.0063	T
GERP RS		-8.9
Varity_R		0.035
gMVP		0.12

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

LitVar

Other links and lift over

dbSNP: rs4740; hg19: chr19-4236996; COSMIC: COSV55689509; COSMIC: COSV55689509;