1-159306030-G-A

Variant names:

• chr1-159306030-G-A
• NM_001387280.1:c.374G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001387280.1(FCER1A):​c.374G>A​(p.Gly125Asp) 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 1,461,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G125V) 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: 2.91

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_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER1A	NM_001387280.1	c.374G>A	p.Gly125Asp	missense_variant	Exon 4 of 5	ENST00000693622.1	NP_001374209.1
FCER1A	NM_002001.4	c.374G>A	p.Gly125Asp	missense_variant	Exon 6 of 7		NP_001992.1
FCER1A	NM_001387282.1	c.275G>A	p.Gly92Asp	missense_variant	Exon 4 of 5		NP_001374211.1
FCER1A	NM_001387281.1	c.119G>A	p.Gly40Asp	missense_variant	Exon 3 of 4		NP_001374210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCER1A	ENST00000693622.1	c.374G>A	p.Gly125Asp	missense_variant	Exon 4 of 5		NM_001387280.1	ENSP00000509626.1
FCER1A	ENST00000368115.5	c.374G>A	p.Gly125Asp	missense_variant	Exon 5 of 6	1		ENSP00000357097.1
FCER1A	ENST00000368114.1	c.275G>A	p.Gly92Asp	missense_variant	Exon 4 of 5	3		ENSP00000357096.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461600 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727096

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.29
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;.
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	3.6	H;.
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.6	D;D
REVEL	Benign	0.23
Sift	Benign	0.037	D;D
Sift4G	Benign	0.063	T;T
Polyphen		1.0	D;.
Vest4		0.69
MutPred		0.84		Loss of catalytic residue at L130 (P = 0.2121);.;
MVP		0.60
MPC		0.22
ClinPred		0.89	D
GERP RS		3.9
Varity_R		0.24
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr1-159275820;