1-159307882-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001387280.1(FCER1A):​c.724G>T​(p.Gly242Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,613,372 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G242A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00042 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 1 hom. )

Consequence

FCER1A
NM_001387280.1 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.513
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.013543725).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FCER1ANM_001387280.1 linkuse as main transcriptc.724G>T p.Gly242Cys missense_variant 5/5 ENST00000693622.1
FCER1ANM_002001.4 linkuse as main transcriptc.724G>T p.Gly242Cys missense_variant 7/7
FCER1ANM_001387282.1 linkuse as main transcriptc.625G>T p.Gly209Cys missense_variant 5/5
FCER1ANM_001387281.1 linkuse as main transcriptc.469G>T p.Gly157Cys missense_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FCER1AENST00000693622.1 linkuse as main transcriptc.724G>T p.Gly242Cys missense_variant 5/5 NM_001387280.1 P1
FCER1AENST00000368115.5 linkuse as main transcriptc.724G>T p.Gly242Cys missense_variant 6/61 P1
FCER1AENST00000368114.1 linkuse as main transcriptc.625G>T p.Gly209Cys missense_variant 5/53

Frequencies

GnomAD3 genomes
AF:
0.000381
AC:
58
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00135
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000104
AC:
26
AN:
250966
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135622
show subpopulations
Gnomad AFR exome
AF:
0.00148
Gnomad AMR exome
AF:
0.0000289
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:
0.000164
GnomAD4 exome
AF:
0.0000329
AC:
48
AN:
1461086
Hom.:
1
Cov.:
30
AF XY:
0.0000261
AC XY:
19
AN XY:
726794
show subpopulations
Gnomad4 AFR exome
AF:
0.00114
Gnomad4 AMR exome
AF:
0.0000895
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:
0.00
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.000420
AC:
64
AN:
152286
Hom.:
1
Cov.:
32
AF XY:
0.000497
AC XY:
37
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.00149
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000748
Hom.:
0
Bravo
AF:
0.000446
ESP6500AA
AF:
0.00136
AC:
6
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000132
AC:
16
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

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 submitterclinical testingAmbry GeneticsSep 14, 2021The c.724G>T (p.G242C) alteration is located in exon 7 (coding exon 5) of the FCER1A gene. This alteration results from a G to T substitution at nucleotide position 724, causing the glycine (G) at amino acid position 242 to be replaced by a cysteine (C). 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
0.29
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.40
T;.
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.65
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.51
T;T
M_CAP
Benign
0.0078
T
MetaRNN
Benign
0.014
T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Uncertain
2.1
M;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.26
T
PROVEAN
Uncertain
-2.7
D;D
REVEL
Benign
0.088
Sift
Uncertain
0.0070
D;D
Sift4G
Benign
0.12
T;T
Polyphen
1.0
D;.
Vest4
0.23
MVP
0.38
MPC
0.19
ClinPred
0.074
T
GERP RS
-0.34
Varity_R
0.13
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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.

Other links and lift over

dbSNP: rs146511084; hg19: chr1-159277672; COSMIC: COSV63667707; API