rs41264475

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001387280.1(FCER1A):c.741C>A(p.Asn247Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00944 in 1,611,768 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0096 ( 92 hom. )

Consequence

FCER1A
NM_001387280.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.187

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00555709).

BP6

Variant 1-159307899-C-A is Benign according to our data. Variant chr1-159307899-C-A is described in ClinVar as [Benign]. Clinvar id is 774399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER1A	NM_001387280.1 link	c.741C>A	p.Asn247Lys	missense_variant	Exon 5 of 5	ENST00000693622.1	NP_001374209.1
FCER1A	NM_002001.4 link	c.741C>A	p.Asn247Lys	missense_variant	Exon 7 of 7		NP_001992.1	P12319
FCER1A	NM_001387282.1 link	c.642C>A	p.Asn214Lys	missense_variant	Exon 5 of 5		NP_001374211.1
FCER1A	NM_001387281.1 link	c.486C>A	p.Asn162Lys	missense_variant	Exon 4 of 4		NP_001374210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FCER1A	ENST00000693622.1 link	c.741C>A	p.Asn247Lys	missense_variant	Exon 5 of 5		NM_001387280.1	ENSP00000509626.1	P12319
FCER1A	ENST00000368115.5 link	c.741C>A	p.Asn247Lys	missense_variant	Exon 6 of 6	1		ENSP00000357097.1	P12319
FCER1A	ENST00000368114.1 link	c.642C>A	p.Asn214Lys	missense_variant	Exon 5 of 5	3		ENSP00000357096.1	E9PRN1

Frequencies

GnomAD3 genomes

AF:

0.00752

AC:

1145

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00695

AC:

1742

AN:

250810

Hom.:

AF XY:

0.00718

AC XY:

973

AN XY:

135570

show subpopulations

Gnomad AFR exome

AF:

0.00301

Gnomad AMR exome

AF:

0.0108

Gnomad ASJ exome

AF:

0.00527

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00121

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.0105

GnomAD4 exome

AF:

0.00964

AC:

14074

AN:

1459448

Hom.:

Cov.:

AF XY:

0.00937

AC XY:

6799

AN XY:

725754

show subpopulations

Gnomad4 AFR exome

AF:

0.00278

Gnomad4 AMR exome

AF:

0.0112

Gnomad4 ASJ exome

AF:

0.00495

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00135

Gnomad4 FIN exome

AF:

0.00221

Gnomad4 NFE exome

AF:

0.0113

Gnomad4 OTH exome

AF:

0.00942

GnomAD4 genome

AF:

0.00753

AC:

1147

AN:

152320

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

526

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00238

Gnomad4 AMR

AF:

0.0139

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.0111

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.00896

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0122

AC:

105

ExAC

AF:

0.00644

AC:

782

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.43

DANN

Benign

0.68

DEOGEN2

Benign

0.20

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.28

T;T

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.59

N;N

REVEL

Benign

0.045

Sift

Benign

0.046

D;D

Sift4G

Uncertain

0.044

D;D

Polyphen

0.0020

B;.

Vest4

0.017

MutPred

0.31

Gain of methylation at N247 (P = 0.0087);.;

MVP

0.19

MPC

0.026

ClinPred

0.0019

GERP RS

-1.5

Varity_R

0.067

gMVP

0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over