Genetic Variant FCER1A:p.Val168Gly (chr1-159306159-T-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001387280.1(FCER1A):c.503T>G(p.Val168Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 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. V168A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

FCER1A
NM_001387280.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.35

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER1A	NM_001387280.1 link	c.503T>G	p.Val168Gly	missense_variant	Exon 4 of 5	ENST00000693622.1	NP_001374209.1
FCER1A	NM_002001.4 link	c.503T>G	p.Val168Gly	missense_variant	Exon 6 of 7		NP_001992.1	P12319
FCER1A	NM_001387282.1 link	c.404T>G	p.Val135Gly	missense_variant	Exon 4 of 5		NP_001374211.1
FCER1A	NM_001387281.1 link	c.248T>G	p.Val83Gly	missense_variant	Exon 3 of 4		NP_001374210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FCER1A	ENST00000693622.1 link	c.503T>G	p.Val168Gly	missense_variant	Exon 4 of 5		NM_001387280.1	ENSP00000509626.1	P12319
FCER1A	ENST00000368115.5 link	c.503T>G	p.Val168Gly	missense_variant	Exon 5 of 6	1		ENSP00000357097.1	P12319
FCER1A	ENST00000368114.1 link	c.404T>G	p.Val135Gly	missense_variant	Exon 4 of 5	3		ENSP00000357096.1	E9PRN1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152192

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:

0.000386

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:

0.0000119

AC:

AN:

251322

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

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:

0.00000274

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.6

L;.

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.068

Sift

Benign

0.29

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.067

B;.

Vest4

0.20

MutPred

0.43

Gain of disorder (P = 0.0046);.;

MVP

0.10

MPC

0.042

ClinPred

0.063

GERP RS

-9.9

Varity_R

0.43

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.37

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.37

Position offset: 0

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