NM_001387280.1:c.725G>A

Variant names:

• chr1-159307883-G-A
• rs201635034
• NM_001387280.1:c.725G>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.725G>A​(p.Gly242Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G242A) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: FCER1A NM_001387280.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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=0.059365958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER1A	NM_001387280.1	c.725G>A	p.Gly242Asp	missense_variant	Exon 5 of 5	ENST00000693622.1	NP_001374209.1
FCER1A	NM_002001.4	c.725G>A	p.Gly242Asp	missense_variant	Exon 7 of 7		NP_001992.1
FCER1A	NM_001387282.1	c.626G>A	p.Gly209Asp	missense_variant	Exon 5 of 5		NP_001374211.1
FCER1A	NM_001387281.1	c.470G>A	p.Gly157Asp	missense_variant	Exon 4 of 4		NP_001374210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCER1A	ENST00000693622.1	c.725G>A	p.Gly242Asp	missense_variant	Exon 5 of 5		NM_001387280.1	ENSP00000509626.1
FCER1A	ENST00000368115.5	c.725G>A	p.Gly242Asp	missense_variant	Exon 6 of 6	1		ENSP00000357097.1
FCER1A	ENST00000368114.1	c.626G>A	p.Gly209Asp	missense_variant	Exon 5 of 5	3		ENSP00000357096.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152142 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74312

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.95	N;N
REVEL	Benign	0.021
Sift	Benign	0.21	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.36	B;.
Vest4		0.11
MutPred		0.37		Loss of MoRF binding (P = 0.0626);.;
MVP		0.31
MPC		0.15
ClinPred		0.12	T
GERP RS		-1.8
Varity_R		0.042
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs201635034; hg19: chr1-159277673;