1-159306030-G-T

Variant names:

• chr1-159306030-G-T
• rs767306097
• NM_001387280.1:c.374G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001387280.1(FCER1A):​c.374G>T​(p.Gly125Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: FCER1A NM_001387280.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.91
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.977

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.374G>T	p.Gly125Val	missense	Exon 4 of 5	NP_001374209.1	P12319
	FCER1A	NM_002001.4		c.374G>T	p.Gly125Val	missense	Exon 6 of 7	NP_001992.1	P12319
	FCER1A	NM_001387282.1		c.275G>T	p.Gly92Val	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.374G>T	p.Gly125Val	missense	Exon 4 of 5	ENSP00000509626.1	P12319
	FCER1A	ENST00000368115.5	TSL:1	c.374G>T	p.Gly125Val	missense	Exon 5 of 6	ENSP00000357097.1	P12319
	FCER1A	ENST00000368114.1	TSL:3	c.275G>T	p.Gly92Val	missense	Exon 4 of 5	ENSP00000357096.1	E9PRN1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251128 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 32 AN: 1461600 Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16 AN XY: 727096

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111828

Other (OTH) AF: 0.0000497 AC: 3 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

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	0.85
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.38
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		2.9
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-7.8	D
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.74
MutPred		0.82		Loss of catalytic residue at L130 (P = 0.1888)
MVP		0.60
MPC		0.22
ClinPred		0.95	D
GERP RS		3.9
Varity_R		0.49
gMVP		0.81
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs767306097; hg19: chr1-159275820;