Variant 1-159306186-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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. 12/20 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, single submitter B:1

Conservation

PhyloP100: -3.85

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 -14 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 id is 770117.Status of the report is criteria_provided_single_submitter, 1 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FCER1A	NM_001387280.1 linkuse as main transcript	c.530C>T	p.Thr177Met	missense_variant	4/5	ENST00000693622.1
FCER1A	NM_002001.4 linkuse as main transcript	c.530C>T	p.Thr177Met	missense_variant	6/7
FCER1A	NM_001387282.1 linkuse as main transcript	c.431C>T	p.Thr144Met	missense_variant	4/5
FCER1A	NM_001387281.1 linkuse as main transcript	c.275C>T	p.Thr92Met	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FCER1A	ENST00000693622.1 linkuse as main transcript	c.530C>T	p.Thr177Met	missense_variant	4/5		NM_001387280.1	P1
FCER1A	ENST00000368115.5 linkuse as main transcript	c.530C>T	p.Thr177Met	missense_variant	5/6	1		P1
FCER1A	ENST00000368114.1 linkuse as main transcript	c.431C>T	p.Thr144Met	missense_variant	4/5	3

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

GnomAD3 exomes

AF:

0.00612

AC:

1537

AN:

251184

Hom.:

AF XY:

0.00570

AC XY:

774

AN XY:

135796

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 SAS exome

AF:

0.00755

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

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.0191

Gnomad4 ASJ exome

AF:

0.00417

Gnomad4 EAS exome

AF:

0.0219

Gnomad4 SAS exome

AF:

0.00647

Gnomad4 FIN exome

AF:

0.000674

Gnomad4 NFE exome

AF:

0.000192

Gnomad4 OTH exome

AF:

0.00475

GnomAD4 genome

AF:

0.00283

AC:

431

AN:

152270

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0263

Gnomad4 SAS

AF:

0.00789

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00149

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.049

DANN

Benign

0.97

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.40

T;T

MetaRNN

Benign

0.0091

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.18

Sift

Benign

0.030

D;D

Sift4G

Benign

0.097

T;T

Polyphen

0.46

P;.

Vest4

0.14

MVP

0.10

MPC

0.048

ClinPred

0.037

GERP RS

-9.9

Varity_R

0.12

gMVP

0.41

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