Genetic Variant FCER1A:p.Thr177Met (chr1-159306186-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001387280.1(FCER1A):c.530C>T(p.Thr177Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,613,916 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 31 hom. )

Consequence

FCER1A
NM_001387280.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.85

Publications

9 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=0.009090602).

BP6

Variant 1-159306186-C-T is Benign according to our data. Variant chr1-159306186-C-T is described in ClinVar as Benign. ClinVar VariationId is 770117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00283 (431/152270) while in subpopulation EAS AF = 0.0263 (136/5178). AF 95% confidence interval is 0.0227. There are 8 homozygotes in GnomAd4. There are 207 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

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	UniProt
FCER1A	NM_001387280.1	MANE Select	c.530C>T	p.Thr177Met	missense	Exon 4 of 5	NP_001374209.1	P12319
FCER1A	NM_002001.4		c.530C>T	p.Thr177Met	missense	Exon 6 of 7	NP_001992.1	P12319
FCER1A	NM_001387282.1		c.431C>T	p.Thr144Met	missense	Exon 4 of 5	NP_001374211.1	E9PRN1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCER1A	ENST00000693622.1	MANE Select	c.530C>T	p.Thr177Met	missense	Exon 4 of 5	ENSP00000509626.1	P12319
FCER1A	ENST00000368115.5	TSL:1	c.530C>T	p.Thr177Met	missense	Exon 5 of 6	ENSP00000357097.1	P12319
FCER1A	ENST00000368114.1	TSL:3	c.431C>T	p.Thr144Met	missense	Exon 4 of 5	ENSP00000357096.1	E9PRN1

Frequencies

GnomAD3 genomes

AF:

0.00279

AC:

425

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0262

Gnomad SAS

AF:

0.00789

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00573

GnomAD2 exomes

AF:

0.00612

AC:

1537

AN:

251184

AF XY:

0.00570

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.0195

Gnomad ASJ exome

AF:

0.00387

Gnomad EAS exome

AF:

0.0267

Gnomad FIN exome

AF:

0.000924

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.00620

GnomAD4 exome

AF:

0.00203

AC:

2964

AN:

1461646

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

1492

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

33472

American (AMR)

AF:

0.0191

AC:

854

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00417

AC:

109

AN:

26130

East Asian (EAS)

AF:

0.0219

AC:

868

AN:

39692

South Asian (SAS)

AF:

0.00647

AC:

558

AN:

86244

European-Finnish (FIN)

AF:

0.000674

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000192

AC:

214

AN:

1111816

Other (OTH)

AF:

0.00475

AC:

287

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

180

360

541

721

901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.00283

AC:

431

AN:

152270

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00118

AC:

AN:

41558

American (AMR)

AF:

0.0109

AC:

166

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3468

East Asian (EAS)

AF:

0.0263

AC:

136

AN:

5178

South Asian (SAS)

AF:

0.00789

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68020

Other (OTH)

AF:

0.00567

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

111

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:

0.00198

Hom.:

Bravo

AF:

0.00374

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00540

AC:

656

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

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

Benign

0.13

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.049

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.21

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0091

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

-3.9

PrimateAI

Benign

0.23

PROVEAN

Benign

-2.2

REVEL

Benign

0.18

Sift

Benign

0.030

Sift4G

Benign

0.097

Polyphen

0.46

Vest4

0.14

MVP

0.10

MPC

0.048

ClinPred

0.037

GERP RS

-9.9

Varity_R

0.12

gMVP

0.41

Mutation Taster

=97/3

polymorphism

(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

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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

Computational scores

Splicing

Publications

Other links and lift over