rs2298804

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001387280.1(FCER1A):c.251A>G(p.Lys84Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,614,048 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0030 ( 20 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 125 hom. )

Consequence

FCER1A
NM_001387280.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.88

Variant links:

Genes affected

FCER1A (HGNC:3609): (Fc epsilon receptor Ia) The immunoglobulin epsilon receptor (IgE receptor) is the initiator of the allergic response. When two or more high-affinity IgE receptors are brought together by allergen-bound IgE molecules, mediators such as histamine that are responsible for allergy symptoms are released. This receptor is comprised of an alpha subunit, a beta subunit, and two gamma subunits. The protein encoded by this gene represents the alpha subunit. [provided by RefSeq, Aug 2011]

FCER1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022898018).

BP6

Variant 1-159304102-A-G is Benign according to our data. Variant chr1-159304102-A-G is described in ClinVar as [Benign]. Clinvar id is 780087.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FCER1A	NM_001387280.1 linkuse as main transcript	c.251A>G	p.Lys84Arg	missense_variant	3/5	ENST00000693622.1
FCER1A	NM_002001.4 linkuse as main transcript	c.251A>G	p.Lys84Arg	missense_variant	5/7
FCER1A	NM_001387282.1 linkuse as main transcript	c.152A>G	p.Lys51Arg	missense_variant	3/5
FCER1A	NM_001387281.1 linkuse as main transcript	c.76+1228A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FCER1A	ENST00000693622.1 linkuse as main transcript	c.251A>G	p.Lys84Arg	missense_variant	3/5		NM_001387280.1	P1
FCER1A	ENST00000368115.5 linkuse as main transcript	c.251A>G	p.Lys84Arg	missense_variant	4/6	1		P1
FCER1A	ENST00000368114.1 linkuse as main transcript	c.152A>G	p.Lys51Arg	missense_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.00298

AC:

453

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0751

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00656

AC:

1646

AN:

250980

Hom.:

AF XY:

0.00592

AC XY:

803

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0857

Gnomad SAS exome

AF:

0.00121

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00174

AC:

2543

AN:

1461742

Hom.:

125

Cov.:

AF XY:

0.00165

AC XY:

1203

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0484

Gnomad4 SAS exome

AF:

0.00112

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.00810

GnomAD4 genome

AF:

0.00296

AC:

451

AN:

152306

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

231

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0749

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00243

Hom.:

Bravo

AF:

0.00300

ExAC

AF:

0.00596

AC:

724

Asia WGS

AF:

0.0310

AC:

108

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.91

Cadd

Benign

0.0010

Dann

Benign

0.20

DEOGEN2

Benign

0.087

T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.15

T;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.14

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

0.16

N;N

REVEL

Benign

0.019

Sift

Benign

0.99

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.0

B;.

Vest4

0.032

MVP

0.23

MPC

0.022

ClinPred

0.014

GERP RS

-7.4

Varity_R

0.059

gMVP

0.28

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