1-159304035-A-C

Variant names:

• chr1-159304035-A-C
• NM_001387280.1:c.184A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001387280.1(FCER1A):​c.184A>C​(p.Thr62Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 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. T62A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FCER1A NM_001387280.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER1A	NM_001387280.1	c.184A>C	p.Thr62Pro	missense_variant	Exon 3 of 5	ENST00000693622.1	NP_001374209.1
FCER1A	NM_002001.4	c.184A>C	p.Thr62Pro	missense_variant	Exon 5 of 7		NP_001992.1
FCER1A	NM_001387282.1	c.85A>C	p.Thr29Pro	missense_variant	Exon 3 of 5		NP_001374211.1
FCER1A	NM_001387281.1	c.76+1161A>C		intron_variant	Intron 2 of 3		NP_001374210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCER1A	ENST00000693622.1	c.184A>C	p.Thr62Pro	missense_variant	Exon 3 of 5		NM_001387280.1	ENSP00000509626.1
FCER1A	ENST00000368115.5	c.184A>C	p.Thr62Pro	missense_variant	Exon 4 of 6	1		ENSP00000357097.1
FCER1A	ENST00000368114.1	c.85A>C	p.Thr29Pro	missense_variant	Exon 3 of 5	3		ENSP00000357096.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461800 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Uncertain	0.47	T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.21	T;T
M_CAP	Benign	0.0076	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.4	M;.
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Benign	0.087
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.93	P;.
Vest4		0.35
MutPred		0.71		Loss of stability (P = 0.0518);.;
MVP		0.56
MPC		0.21
ClinPred		0.71	D
GERP RS		2.2
Varity_R		0.81
gMVP		0.77

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-159273825;