1-159306227-A-C

Variant names:

• chr1-159306227-A-C
• rs1369783246
• NM_001387280.1:c.571A>C

Variant summary

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

The NM_001387280.1(FCER1A):​c.571A>C​(p.Asn191His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,514 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FCER1A NM_001387280.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.138

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=0.1262384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER1A	NM_001387280.1	c.571A>C	p.Asn191His	missense_variant	Exon 4 of 5	ENST00000693622.1	NP_001374209.1
FCER1A	NM_002001.4	c.571A>C	p.Asn191His	missense_variant	Exon 6 of 7		NP_001992.1
FCER1A	NM_001387282.1	c.472A>C	p.Asn158His	missense_variant	Exon 4 of 5		NP_001374211.1
FCER1A	NM_001387281.1	c.316A>C	p.Asn106His	missense_variant	Exon 3 of 4		NP_001374210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCER1A	ENST00000693622.1	c.571A>C	p.Asn191His	missense_variant	Exon 4 of 5		NM_001387280.1	ENSP00000509626.1
FCER1A	ENST00000368115.5	c.571A>C	p.Asn191His	missense_variant	Exon 5 of 6	1		ENSP00000357097.1
FCER1A	ENST00000368114.1	c.472A>C	p.Asn158His	missense_variant	Exon 4 of 5	3		ENSP00000357096.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461514 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727022

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.571A>C (p.N191H) alteration is located in exon 6 (coding exon 4) of the FCER1A gene. This alteration results from a A to C substitution at nucleotide position 571, causing the asparagine (N) at amino acid position 191 to be replaced by a histidine (H). 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	0.086
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.34	T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.029
Sift	Uncertain	0.017	D;D
Sift4G	Benign	0.20	T;T
Polyphen		0.010	B;.
Vest4		0.19
MutPred		0.29		Loss of stability (P = 0.0921);.;
MVP		0.33
MPC		0.18
ClinPred		0.33	T
GERP RS		-2.0
Varity_R		0.25
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1369783246; hg19: chr1-159276017;