1-159306071-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001387280.1(FCER1A):c.415G>A(p.Asp139Asn) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FCER1A NM_001387280.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.840

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033930182).
• BP6: Variant 1-159306071-G-A is Benign according to our data. Variant chr1-159306071-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2253091.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCER1A	NM_001387280.1	c.415G>A	p.Asp139Asn	missense_variant	4/5	ENST00000693622.1
FCER1A	NM_002001.4	c.415G>A	p.Asp139Asn	missense_variant	6/7
FCER1A	NM_001387282.1	c.316G>A	p.Asp106Asn	missense_variant	4/5
FCER1A	NM_001387281.1	c.160G>A	p.Asp54Asn	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCER1A	ENST00000693622.1	c.415G>A	p.Asp139Asn	missense_variant	4/5		NM_001387280.1	P1
FCER1A	ENST00000368115.5	c.415G>A	p.Asp139Asn	missense_variant	5/6	1		P1
FCER1A	ENST00000368114.1	c.316G>A	p.Asp106Asn	missense_variant	4/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.019
Dann	Benign	0.47
DEOGEN2	Benign	0.079	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.034	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.76	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.69	N;N
REVEL	Benign	0.0050
Sift	Benign	0.75	T;T
Sift4G	Benign	0.65	T;T
Polyphen		0.0	B;.
Vest4		0.074
MutPred		0.49		Gain of MoRF binding (P = 0.0296);.;
MVP		0.15
MPC		0.024
ClinPred		0.032	T
GERP RS		-3.0
Varity_R		0.30
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr1-159275861; COSMIC: COSV104677916;