Variant chr1-159306071-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.840

Variant links:

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]

FCER1A links:

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ACMG classification

Classification made for transcript

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	Protein
FCER1A	NM_001387280.1 linkuse as main transcript	c.415G>A	p.Asp139Asn	missense_variant	4/5	ENST00000693622.1	NP_001374209.1
FCER1A	NM_002001.4 linkuse as main transcript	c.415G>A	p.Asp139Asn	missense_variant	6/7		NP_001992.1
FCER1A	NM_001387282.1 linkuse as main transcript	c.316G>A	p.Asp106Asn	missense_variant	4/5		NP_001374211.1
FCER1A	NM_001387281.1 linkuse as main transcript	c.160G>A	p.Asp54Asn	missense_variant	3/4		NP_001374210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
FCER1A	ENST00000693622.1 linkuse as main transcript	c.415G>A	p.Asp139Asn	missense_variant	4/5		NM_001387280.1	ENSP00000509626	P1
FCER1A	ENST00000368115.5 linkuse as main transcript	c.415G>A	p.Asp139Asn	missense_variant	5/6	1		ENSP00000357097	P1
FCER1A	ENST00000368114.1 linkuse as main transcript	c.316G>A	p.Asp106Asn	missense_variant	4/5	3		ENSP00000357096

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

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

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.76

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over