Variant rs2228137 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001220500.2(FCER2):c.184C>T(p.Arg62Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,608,806 control chromosomes in the GnomAD database, including 20,203 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.18 ( 3149 hom., cov: 31)

Exomes 𝑓: 0.14 ( 17054 hom. )

Consequence

FCER2
NM_001220500.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50

Variant links:

Genes affected

FCER2 (HGNC:3612): (Fc epsilon receptor II) The protein encoded by this gene is a B-cell specific antigen, and a low-affinity receptor for IgE. It has essential roles in B cell growth and differentiation, and the regulation of IgE production. This protein also exists as a soluble secreted form, then functioning as a potent mitogenic growth factor. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]

FCER2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065580606).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FCER2	NM_001220500.2 linkuse as main transcript	c.184C>T	p.Arg62Trp	missense_variant	4/11	ENST00000597921.6	NP_001207429.1
FCER2	NM_002002.5 linkuse as main transcript	c.184C>T	p.Arg62Trp	missense_variant	4/11		NP_001993.2
FCER2	NM_001207019.3 linkuse as main transcript	c.181C>T	p.Arg61Trp	missense_variant	3/10		NP_001193948.2
FCER2	XM_005272462.5 linkuse as main transcript	c.184C>T	p.Arg62Trp	missense_variant	4/11		XP_005272519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCER2	ENST00000597921.6 linkuse as main transcript	c.184C>T	p.Arg62Trp	missense_variant	4/11	1	NM_001220500.2	ENSP00000471974	P2

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27945

AN:

151854

Hom.:

3145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.0722

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.171

GnomAD3 exomes

AF:

0.152

AC:

37873

AN:

249346

Hom.:

3516

AF XY:

0.156

AC XY:

21030

AN XY:

134692

show subpopulations

Gnomad AFR exome

AF:

0.315

Gnomad AMR exome

AF:

0.0795

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.0800

Gnomad SAS exome

AF:

0.252

Gnomad FIN exome

AF:

0.116

Gnomad NFE exome

AF:

0.142

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.145

AC:

211144

AN:

1456834

Hom.:

17054

Cov.:

AF XY:

0.148

AC XY:

107160

AN XY:

724732

show subpopulations

Gnomad4 AFR exome

AF:

0.319

Gnomad4 AMR exome

AF:

0.0845

Gnomad4 ASJ exome

AF:

0.156

Gnomad4 EAS exome

AF:

0.0551

Gnomad4 SAS exome

AF:

0.245

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.156

GnomAD4 genome

AF:

0.184

AC:

27984

AN:

151972

Hom.:

3149

Cov.:

AF XY:

0.183

AC XY:

13605

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.308

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.156

Gnomad4 EAS

AF:

0.0724

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.170

Alfa

AF:

0.142

Hom.:

4328

Bravo

AF:

0.185

TwinsUK

AF:

0.154

AC:

572

ALSPAC

AF:

0.146

AC:

562

ESP6500AA

AF:

0.300

AC:

1324

ESP6500EA

AF:

0.141

AC:

1214

ExAC

AF:

0.161

AC:

19599

EpiCase

AF:

0.140

EpiControl

AF:

0.143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

.;T;T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.76

T;.;T;T

MetaRNN

Benign

0.0066

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.0

.;L;L;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.5

N;N;.;.

REVEL

Benign

0.10

Sift

Uncertain

0.0070

D;D;.;.

Sift4G

Uncertain

0.019

D;D;D;D

Polyphen

0.97

.;D;D;.

Vest4

0.11

MPC

0.082

ClinPred

0.014

GERP RS

3.2

Varity_R

0.091

gMVP

0.24

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over