chr1-159306130-C-A

Variant names:

• chr1-159306130-C-A
• rs767348260
• NM_001387280.1:c.474C>A

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.474C>A​(p.Asn158Lys) 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. 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: -0.0360
• 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=0.16118723).

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.474C>A	p.Asn158Lys	missense	Exon 4 of 5	NP_001374209.1	P12319
	FCER1A	NM_002001.4		c.474C>A	p.Asn158Lys	missense	Exon 6 of 7	NP_001992.1	P12319
	FCER1A	NM_001387282.1		c.375C>A	p.Asn125Lys	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.474C>A	p.Asn158Lys	missense	Exon 4 of 5	ENSP00000509626.1	P12319
	FCER1A	ENST00000368115.5	TSL:1	c.474C>A	p.Asn158Lys	missense	Exon 5 of 6	ENSP00000357097.1	P12319
	FCER1A	ENST00000368114.1	TSL:3	c.375C>A	p.Asn125Lys	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	Pathogenic	0.60
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.036
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.081
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.019	D
Polyphen		0.90	P
Vest4		0.35
MutPred		0.52		Gain of methylation at N158 (P = 0.0126)
MVP		0.33
MPC		0.12
ClinPred		0.96	D
GERP RS		1.7
Varity_R		0.68
gMVP		0.29
Mutation Taster		=80/20	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: rs767348260; hg19: chr1-159275920;