Genetic Variant NM_001220500.2:c.458A>G (chr19-7696836-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001220500.2(FCER2):c.458A>G(p.Gln153Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,425,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. Q153P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FCER2
NM_001220500.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0470

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02558139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER2	NM_001220500.2 link	c.458A>G	p.Gln153Arg	missense_variant	Exon 8 of 11	ENST00000597921.6	NP_001207429.1	P06734
FCER2	NM_002002.5 link	c.458A>G	p.Gln153Arg	missense_variant	Exon 8 of 11		NP_001993.2	P06734
FCER2	NM_001207019.3 link	c.455A>G	p.Gln152Arg	missense_variant	Exon 7 of 10		NP_001193948.2	P06734K3W4U1
FCER2	XM_005272462.5 link	c.458A>G	p.Gln153Arg	missense_variant	Exon 8 of 11		XP_005272519.1	P06734

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCER2	ENST00000597921.6 link	c.458A>G	p.Gln153Arg	missense_variant	Exon 8 of 11	1	NM_001220500.2	ENSP00000471974.1		P06734

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1425846

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

705494

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32994

American (AMR)

AF:

0.00

AC:

AN:

39086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25464

East Asian (EAS)

AF:

0.00

AC:

AN:

38376

South Asian (SAS)

AF:

0.00

AC:

AN:

81300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1092876

Other (OTH)

AF:

0.00

AC:

AN:

59102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.5

(source)

DANN

Benign

0.25

DEOGEN2

Benign

0.017

.;T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.30

T;.;T;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.026

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.76

.;N;N;.

PhyloP100

0.047

PrimateAI

Benign

0.23

PROVEAN

Benign

0.20

N;N;.;.

REVEL

Benign

0.011

Sift

Benign

0.68

T;T;.;.

Sift4G

Benign

0.84

T;T;T;T

Polyphen

0.0010

.;B;B;.

Vest4

0.11

MutPred

0.34

.;Gain of MoRF binding (P = 0.0294);Gain of MoRF binding (P = 0.0294);.;

MVP

0.22

MPC

0.075

ClinPred

0.018

GERP RS

-4.6

Varity_R

0.028

gMVP

0.28

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over