chr1-159306041-T-A

Position:

• chr1-159306041-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001387280.1(FCER1A):​c.385T>A​(p.Phe129Ile) 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. 15/21 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)
• Consequence: FCER1A NM_001387280.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.99

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05817002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCER1A	NM_001387280.1	c.385T>A	p.Phe129Ile	missense_variant	4/5	ENST00000693622.1
FCER1A	NM_002001.4	c.385T>A	p.Phe129Ile	missense_variant	6/7
FCER1A	NM_001387282.1	c.286T>A	p.Phe96Ile	missense_variant	4/5
FCER1A	NM_001387281.1	c.130T>A	p.Phe44Ile	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCER1A	ENST00000693622.1	c.385T>A	p.Phe129Ile	missense_variant	4/5		NM_001387280.1	P1
FCER1A	ENST00000368115.5	c.385T>A	p.Phe129Ile	missense_variant	5/6	1		P1
FCER1A	ENST00000368114.1	c.286T>A	p.Phe96Ile	missense_variant	4/5	3

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

Jun 28, 2022

The c.385T>A (p.F129I) alteration is located in exon 6 (coding exon 4) of the FCER1A gene. This alteration results from a T to A substitution at nucleotide position 385, causing the phenylalanine (F) at amino acid position 129 to be replaced by an isoleucine (I). 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	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.042
DANN	Benign	0.80
DEOGEN2	Benign	0.079	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0094	N
LIST_S2	Benign	0.37	T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.35	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.040	N;N
REVEL	Benign	0.0070
Sift	Benign	0.39	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.14	B;.
Vest4		0.20
MutPred		0.37		Gain of MoRF binding (P = 0.1452);.;
MVP		0.055
MPC		0.032
ClinPred		0.11	T
GERP RS		-9.6
Varity_R		0.14
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr1-159275831;