Variant 1-159304035-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001387280.1(FCER1A):c.184A>G(p.Thr62Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

FCER1A
NM_001387280.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.43

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10562825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCER1A	NM_001387280.1 linkuse as main transcript	c.184A>G	p.Thr62Ala	missense_variant	3/5	ENST00000693622.1	NP_001374209.1
FCER1A	NM_002001.4 linkuse as main transcript	c.184A>G	p.Thr62Ala	missense_variant	5/7		NP_001992.1	P12319
FCER1A	NM_001387282.1 linkuse as main transcript	c.85A>G	p.Thr29Ala	missense_variant	3/5		NP_001374211.1
FCER1A	NM_001387281.1 linkuse as main transcript	c.76+1161A>G		intron_variant			NP_001374210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FCER1A	ENST00000693622.1 linkuse as main transcript	c.184A>G	p.Thr62Ala	missense_variant	3/5		NM_001387280.1	ENSP00000509626.1	P12319
FCER1A	ENST00000368115.5 linkuse as main transcript	c.184A>G	p.Thr62Ala	missense_variant	4/6	1		ENSP00000357097.1	P12319
FCER1A	ENST00000368114.1 linkuse as main transcript	c.85A>G	p.Thr29Ala	missense_variant	3/5	3		ENSP00000357096.1	E9PRN1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251044

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.000123

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

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

AF:

0.0000526

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000567

ExAC

AF:

0.00000824

AC:

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

Oct 26, 2022

The c.184A>G (p.T62A) alteration is located in exon 5 (coding exon 3) of the FCER1A gene. This alteration results from a A to G substitution at nucleotide position 184, causing the threonine (T) at amino acid position 62 to be replaced by an alanine (A). 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

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.1

DANN

Benign

0.81

DEOGEN2

Uncertain

0.45

T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.24

T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

L;.

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.7

D;D

REVEL

Benign

0.036

Sift

Benign

0.091

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.049

B;.

Vest4

0.065

MutPred

0.56

Loss of stability (P = 0.0733);.;

MVP

0.43

MPC

0.029

ClinPred

0.027

GERP RS

2.2

Varity_R

0.35

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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