1-159304102-A-T

Variant names:

• chr1-159304102-A-T
• rs2298804
• NM_001387280.1:c.251A>T

Variant summary

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

The NM_002001.4(FCER1A):​c.251A>T​(p.Lys84Ile) 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 152,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. K84R) has been classified as Benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: FCER1A NM_002001.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.88
• Publications: 12 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=0.09942675).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002001.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCER1A	NM_001387280.1	MANE Select	c.251A>T	p.Lys84Ile	missense	Exon 3 of 5	NP_001374209.1
	FCER1A	NM_002001.4		c.251A>T	p.Lys84Ile	missense	Exon 5 of 7	NP_001992.1
	FCER1A	NM_001387282.1		c.152A>T	p.Lys51Ile	missense	Exon 3 of 5	NP_001374211.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCER1A	ENST00000693622.1	MANE Select	c.251A>T	p.Lys84Ile	missense	Exon 3 of 5	ENSP00000509626.1
	FCER1A	ENST00000368115.5	TSL:1	c.251A>T	p.Lys84Ile	missense	Exon 4 of 6	ENSP00000357097.1
	FCER1A	ENST00000368114.1	TSL:3	c.152A>T	p.Lys51Ile	missense	Exon 3 of 5	ENSP00000357096.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 21

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0030
DANN	Benign	0.87
DEOGEN2	Benign	0.35	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0059	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-5.9
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.055
Sift	Benign	0.090	T
Sift4G	Benign	0.19	T
Polyphen		0.0010	B
Vest4		0.24
MVP		0.15
MPC		0.036
ClinPred		0.17	T
GERP RS		-7.4
Varity_R		0.36
gMVP		0.52
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs2298804; hg19: chr1-159273892;