1-159304051-A-C

Variant names:

• chr1-159304051-A-C
• NM_001387280.1:c.200A>C

Variant summary

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

The NM_001387280.1(FCER1A):​c.200A>C​(p.Asn67Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N67S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FCER1A NM_001387280.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32

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.200A>C	p.Asn67Thr	missense_variant	Exon 3 of 5	ENST00000693622.1	NP_001374209.1
FCER1A	NM_002001.4	c.200A>C	p.Asn67Thr	missense_variant	Exon 5 of 7		NP_001992.1
FCER1A	NM_001387282.1	c.101A>C	p.Asn34Thr	missense_variant	Exon 3 of 5		NP_001374211.1
FCER1A	NM_001387281.1	c.76+1177A>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.200A>C	p.Asn67Thr	missense_variant	Exon 3 of 5		NM_001387280.1	ENSP00000509626.1
FCER1A	ENST00000368115.5	c.200A>C	p.Asn67Thr	missense_variant	Exon 4 of 6	1		ENSP00000357097.1
FCER1A	ENST00000368114.1	c.101A>C	p.Asn34Thr	missense_variant	Exon 3 of 5	3		ENSP00000357096.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727224

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: 0.00000180

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	Uncertain	0.51
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T;.
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	4.2	H;.
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;.
Vest4		0.41
MutPred		0.54		Loss of catalytic residue at N67 (P = 0.0142);.;
MVP		0.51
MPC		0.20
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.90
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-159273841;