Genetic Variant FCER1A:p.Pro254Leu (chr1-159307919-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

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

The NM_001387280.1(FCER1A):c.761C>T(p.Pro254Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,589,846 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 12 hom. )

Consequence

FCER1A
NM_001387280.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.368

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=0.005096704).

BP6

Variant 1-159307919-C-T is Benign according to our data. Variant chr1-159307919-C-T is described in ClinVar as [Benign]. Clinvar id is 785791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER1A	NM_001387280.1 link	c.761C>T	p.Pro254Leu	missense_variant	Exon 5 of 5	ENST00000693622.1	NP_001374209.1
FCER1A	NM_002001.4 link	c.761C>T	p.Pro254Leu	missense_variant	Exon 7 of 7		NP_001992.1	P12319
FCER1A	NM_001387282.1 link	c.662C>T	p.Pro221Leu	missense_variant	Exon 5 of 5		NP_001374211.1
FCER1A	NM_001387281.1 link	c.506C>T	p.Pro169Leu	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.761C>T	p.Pro254Leu	missense_variant	Exon 5 of 5		NM_001387280.1	ENSP00000509626.1	P12319
FCER1A	ENST00000368115.5 link	c.761C>T	p.Pro254Leu	missense_variant	Exon 6 of 6	1		ENSP00000357097.1	P12319
FCER1A	ENST00000368114.1 link	c.662C>T	p.Pro221Leu	missense_variant	Exon 5 of 5	3		ENSP00000357096.1	E9PRN1

Frequencies

GnomAD3 genomes

AF:

0.00140

AC:

213

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.00168

AC:

410

AN:

243372

Hom.:

AF XY:

0.00177

AC XY:

232

AN XY:

131416

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000859

Gnomad ASJ exome

AF:

0.0280

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000350

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000810

Gnomad OTH exome

AF:

0.00339

GnomAD4 exome

AF:

0.00101

AC:

1457

AN:

1437568

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

732

AN XY:

711864

show subpopulations

Gnomad4 AFR exome

AF:

0.000335

Gnomad4 AMR exome

AF:

0.000860

Gnomad4 ASJ exome

AF:

0.0264

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000959

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000489

Gnomad4 OTH exome

AF:

0.00294

GnomAD4 genome

AF:

0.00140

AC:

213

AN:

152278

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

108

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.0323

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000809

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00145

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00126

AC:

153

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.023

Sift

Benign

0.21

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.0050

B;.

Vest4

0.15

MVP

0.19

MPC

0.024

ClinPred

0.015

GERP RS

-0.15

Varity_R

0.035

gMVP

0.34

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