Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001387280.1(FCER1A):c.302G>A(p.Ser101Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,613,892 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 170 hom. )

Consequence

FCER1A
NM_001387280.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.58

Publications

16 publications found

Variant links:

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]

FCER1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032084882).

BP6

Variant 1-159304153-G-A is Benign according to our data. Variant chr1-159304153-G-A is described in ClinVar as Benign. ClinVar VariationId is 787858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0711 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FCER1A	NM_001387280.1	MANE Select	c.302G>A	p.Ser101Asn	missense	Exon 3 of 5	NP_001374209.1
FCER1A	NM_002001.4		c.302G>A	p.Ser101Asn	missense	Exon 5 of 7	NP_001992.1
FCER1A	NM_001387282.1		c.203G>A	p.Ser68Asn	missense	Exon 3 of 5	NP_001374211.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FCER1A	ENST00000693622.1	MANE Select	c.302G>A	p.Ser101Asn	missense	Exon 3 of 5	ENSP00000509626.1
FCER1A	ENST00000368115.5	TSL:1	c.302G>A	p.Ser101Asn	missense	Exon 4 of 6	ENSP00000357097.1
FCER1A	ENST00000368114.1	TSL:3	c.203G>A	p.Ser68Asn	missense	Exon 3 of 5	ENSP00000357096.1

Frequencies

GnomAD3 genomes

AF:

0.00365

AC:

555

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.0775

Gnomad SAS

AF:

0.00641

Gnomad FIN

AF:

0.00216

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00637

AC:

1597

AN:

250848

AF XY:

0.00620

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00239

Gnomad EAS exome

AF:

0.0693

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.000918

Gnomad OTH exome

AF:

0.00458

GnomAD4 exome

AF:

0.00338

AC:

4944

AN:

1461574

Hom.:

170

Cov.:

AF XY:

0.00341

AC XY:

2480

AN XY:

727104

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33478

American (AMR)

AF:

0.000604

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00237

AC:

AN:

26132

East Asian (EAS)

AF:

0.0850

AC:

3373

AN:

39680

South Asian (SAS)

AF:

0.00459

AC:

396

AN:

86256

European-Finnish (FIN)

AF:

0.00135

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00399

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000592

AC:

658

AN:

1111734

Other (OTH)

AF:

0.00543

AC:

328

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

259

518

776

1035

1294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00362

AC:

552

AN:

152318

Hom.:

Cov.:

AF XY:

0.00405

AC XY:

302

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41558

American (AMR)

AF:

0.000589

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3472

East Asian (EAS)

AF:

0.0773

AC:

401

AN:

5186

South Asian (SAS)

AF:

0.00642

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00216

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000779

AC:

AN:

68038

Other (OTH)

AF:

0.00662

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

100

125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00330

Hom.:

Bravo

AF:

0.00387

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00628

AC:

762

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00190

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.74

Eigen

Uncertain

0.44

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.55

MutationAssessor

Pathogenic

4.0

PhyloP100

2.6

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.16

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.48

MVP

0.56

MPC

0.20

ClinPred

0.15

GERP RS

3.8

Varity_R

0.58

gMVP

0.61

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs2298805

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over