Variant 19-4234729-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005755.3(EBI3):c.442C>G(p.Gln148Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

EBI3
NM_005755.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.223

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:

EBI3 (HGNC:):

EBI3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33266217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBI3	NM_005755.3 linkuse as main transcript	c.442C>G	p.Gln148Glu	missense_variant	4/5	ENST00000221847.6	NP_005746.2	Q14213

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBI3	ENST00000221847.6 linkuse as main transcript	c.442C>G	p.Gln148Glu	missense_variant	4/5	1	NM_005755.3	ENSP00000221847.4		Q14213
EBI3	ENST00000599339.1 linkuse as main transcript	n.340C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.442C>G (p.Q148E) alteration is located in exon 4 (coding exon 4) of the EBI3 gene. This alteration results from a C to G substitution at nucleotide position 442, causing the glutamine (Q) at amino acid position 148 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

2.2

DANN

Benign

0.66

DEOGEN2

Benign

0.12

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.48

M_CAP

Benign

0.014

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.72

REVEL

Benign

0.10

Sift

Benign

0.70

Sift4G

Benign

0.70

Polyphen

0.0090

Vest4

0.12

MutPred

0.63

Gain of disorder (P = 0.1062);

MVP

0.41

MPC

0.11

ClinPred

0.041

GERP RS

1.8

Varity_R

0.16

gMVP

0.36

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over