NM_001387280.1:c.406A>G

Variant names:

• chr1-159306062-A-G
• NM_001387280.1:c.406A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001387280.1(FCER1A):​c.406A>G​(p.Arg136Gly) 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. 14/22 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: 2.69
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23477823).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387280.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCER1A	NM_001387280.1	MANE Select	c.406A>G	p.Arg136Gly	missense	Exon 4 of 5	NP_001374209.1	P12319
	FCER1A	NM_002001.4		c.406A>G	p.Arg136Gly	missense	Exon 6 of 7	NP_001992.1	P12319
	FCER1A	NM_001387282.1		c.307A>G	p.Arg103Gly	missense	Exon 4 of 5	NP_001374211.1	E9PRN1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCER1A	ENST00000693622.1	MANE Select	c.406A>G	p.Arg136Gly	missense	Exon 4 of 5	ENSP00000509626.1	P12319
	FCER1A	ENST00000368115.5	TSL:1	c.406A>G	p.Arg136Gly	missense	Exon 5 of 6	ENSP00000357097.1	P12319
	FCER1A	ENST00000368114.1	TSL:3	c.307A>G	p.Arg103Gly	missense	Exon 4 of 5	ENSP00000357096.1	E9PRN1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Uncertain	24
DANN	Benign	0.92
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.7
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.063
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.44	B
Vest4		0.21
MutPred		0.58		Loss of MoRF binding (P = 0.0607)
MVP		0.30
MPC		0.11
ClinPred		0.90	D
GERP RS		2.4
Varity_R		0.54
gMVP		0.60
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr1-159275852;