19-7689371-C-T

Position:

chr19-7689371-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000597921.6(FCER2):c.788G>A(p.Arg263Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,608,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

FCER2
ENST00000597921.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.95

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06542659).

BP6

Variant 19-7689371-C-T is Benign according to our data. Variant chr19-7689371-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2524275.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FCER2	NM_001220500.2 linkuse as main transcript	c.788G>A	p.Arg263Gln	missense_variant	11/11	ENST00000597921.6	NP_001207429.1
FCER2	NM_002002.5 linkuse as main transcript	c.788G>A	p.Arg263Gln	missense_variant	11/11		NP_001993.2
FCER2	NM_001207019.3 linkuse as main transcript	c.785G>A	p.Arg262Gln	missense_variant	10/10		NP_001193948.2
FCER2	XM_005272462.5 linkuse as main transcript	c.788G>A	p.Arg263Gln	missense_variant	11/11		XP_005272519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCER2	ENST00000597921.6 linkuse as main transcript	c.788G>A	p.Arg263Gln	missense_variant	11/11	1	NM_001220500.2	ENSP00000471974	P2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000170

AC:

AN:

234612

Hom.:

AF XY:

0.0000234

AC XY:

AN XY:

128192

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000288

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1456658

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

724382

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.8

DANN

Benign

0.85

DEOGEN2

Benign

0.018

.;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.68

T;.;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.065

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.68

.;N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.77

N;N;.

REVEL

Benign

0.035

Sift

Benign

0.36

T;T;.

Sift4G

Benign

0.45

T;T;T

Polyphen

0.18

.;B;B

Vest4

0.017

MutPred

0.53

.;Loss of MoRF binding (P = 0.0279);Loss of MoRF binding (P = 0.0279);

MVP

0.13

MPC

0.089

ClinPred

0.036

GERP RS

-7.6

Varity_R

0.12

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over