1-159306222-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001387280.1(FCER1A):c.566C>T(p.Pro189Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: FCER1A NM_001387280.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.270

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]

ACMG classification

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=0.19683054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCER1A	NM_001387280.1	c.566C>T	p.Pro189Leu	missense_variant	4/5	ENST00000693622.1
FCER1A	NM_002001.4	c.566C>T	p.Pro189Leu	missense_variant	6/7
FCER1A	NM_001387282.1	c.467C>T	p.Pro156Leu	missense_variant	4/5
FCER1A	NM_001387281.1	c.311C>T	p.Pro104Leu	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCER1A	ENST00000693622.1	c.566C>T	p.Pro189Leu	missense_variant	4/5		NM_001387280.1	P1
FCER1A	ENST00000368115.5	c.566C>T	p.Pro189Leu	missense_variant	5/6	1		P1
FCER1A	ENST00000368114.1	c.467C>T	p.Pro156Leu	missense_variant	4/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461660 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

The c.566C>T (p.P189L) alteration is located in exon 6 (coding exon 4) of the FCER1A gene. This alteration results from a C to T substitution at nucleotide position 566, causing the proline (P) at amino acid position 189 to be replaced by a leucine (L). 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	0.15
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	11
Dann	Benign	0.66
DEOGEN2	Benign	0.24	T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.067
Sift	Uncertain	0.024	D;D
Sift4G	Benign	0.14	T;T
Polyphen		0.94	P;.
Vest4		0.12
MutPred		0.60		Loss of catalytic residue at P189 (P = 0.1837);.;
MVP		0.41
MPC		0.035
ClinPred		0.47	T
GERP RS		0.48
Varity_R		0.12
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-159276012;