chr1-159306130-C-A

Position:

• chr1-159306130-C-A

Variant summary

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

The NM_001387280.1(FCER1A):​c.474C>A​(p.Asn158Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FCER1A NM_001387280.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0360

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=0.16118723).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCER1A	NM_001387280.1	c.474C>A	p.Asn158Lys	missense_variant	4/5	ENST00000693622.1	NP_001374209.1
FCER1A	NM_002001.4	c.474C>A	p.Asn158Lys	missense_variant	6/7		NP_001992.1
FCER1A	NM_001387282.1	c.375C>A	p.Asn125Lys	missense_variant	4/5		NP_001374211.1
FCER1A	NM_001387281.1	c.219C>A	p.Asn73Lys	missense_variant	3/4		NP_001374210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCER1A	ENST00000693622.1	c.474C>A	p.Asn158Lys	missense_variant	4/5		NM_001387280.1	ENSP00000509626	P1
FCER1A	ENST00000368115.5	c.474C>A	p.Asn158Lys	missense_variant	5/6	1		ENSP00000357097	P1
FCER1A	ENST00000368114.1	c.375C>A	p.Asn125Lys	missense_variant	4/5	3		ENSP00000357096

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

May 30, 2023

The c.474C>A (p.N158K) alteration is located in exon 6 (coding exon 4) of the FCER1A gene. This alteration results from a C to A substitution at nucleotide position 474, causing the asparagine (N) at amino acid position 158 to be replaced by a lysine (K). 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	Pathogenic	0.60
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	0.99	N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Benign	0.081
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.019	D;D
Polyphen		0.90	P;.
Vest4		0.35
MutPred		0.52		Gain of methylation at N158 (P = 0.0126);.;
MVP		0.33
MPC		0.12
ClinPred		0.96	D
GERP RS		1.7
Varity_R		0.68
gMVP		0.29

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: chr1-159275920;