Genetic Variant FCER1A:p.Thr62Ser (chr1-159304035-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001387280.1(FCER1A):c.184A>T(p.Thr62Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,614,138 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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. T62A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

FCER1A
NM_001387280.1 missense

Scores

Clinical Significance

Not reported in ClinVar

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.022827536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER1A	NM_001387280.1 link	c.184A>T	p.Thr62Ser	missense_variant	Exon 3 of 5	ENST00000693622.1	NP_001374209.1
FCER1A	NM_002001.4 link	c.184A>T	p.Thr62Ser	missense_variant	Exon 5 of 7		NP_001992.1	P12319
FCER1A	NM_001387282.1 link	c.85A>T	p.Thr29Ser	missense_variant	Exon 3 of 5		NP_001374211.1
FCER1A	NM_001387281.1 link	c.76+1161A>T		intron_variant	Intron 2 of 3		NP_001374210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FCER1A	ENST00000693622.1 link	c.184A>T	p.Thr62Ser	missense_variant	Exon 3 of 5		NM_001387280.1	ENSP00000509626.1	P12319
FCER1A	ENST00000368115.5 link	c.184A>T	p.Thr62Ser	missense_variant	Exon 4 of 6	1		ENSP00000357097.1	P12319
FCER1A	ENST00000368114.1 link	c.85A>T	p.Thr29Ser	missense_variant	Exon 3 of 5	3		ENSP00000357096.1	E9PRN1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000135

AC:

AN:

251044

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000289

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:

0.000185

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000112

AC:

163

AN:

1461800

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000113

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000256

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000855

Hom.:

Bravo

AF:

0.000597

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.5

DANN

Benign

0.75

DEOGEN2

Uncertain

0.44

T;.

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.22

T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.025

Sift

Benign

0.064

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.055

B;.

Vest4

0.12

MutPred

0.67

Gain of disorder (P = 0.026);.;

MVP

0.48

MPC

0.044

ClinPred

0.043

GERP RS

2.2

Varity_R

0.41

gMVP

0.43

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over