chr1-159307899-C-A

Position:

• chr1-159307899-C-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.187

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]

ACMG classification

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/exons	MANE	UniProt
FCER1A	NM_001387280.1	c.741C>A	p.Asn247Lys	missense_variant	5/5	ENST00000693622.1
FCER1A	NM_002001.4	c.741C>A	p.Asn247Lys	missense_variant	7/7
FCER1A	NM_001387282.1	c.642C>A	p.Asn214Lys	missense_variant	5/5
FCER1A	NM_001387281.1	c.486C>A	p.Asn162Lys	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCER1A	ENST00000693622.1	c.741C>A	p.Asn247Lys	missense_variant	5/5		NM_001387280.1	P1
FCER1A	ENST00000368115.5	c.741C>A	p.Asn247Lys	missense_variant	6/6	1		P1
FCER1A	ENST00000368114.1	c.642C>A	p.Asn214Lys	missense_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.00752 AC: 1145 AN: 152202 Hom.: 10 Cov.: 32

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.: 12 AF XY: 0.00718 AC XY: 973 AN XY: 135570

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.: 92 Cov.: 30 AF XY: 0.00937 AC XY: 6799 AN XY: 725754

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.: 10 Cov.: 32 AF XY: 0.00706 AC XY: 526 AN XY: 74482

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.: 21

Bravo AF: 0.00896

TwinsUK AF: 0.0108 AC: 40

ALSPAC AF: 0.0119 AC: 46

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.0122 AC: 105

ExAC AF: 0.00644 AC: 782

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.77	T
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	N
LIST_S2	Benign	0.28	T;T
MetaRNN	Benign	0.0056	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
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	T
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

Other links and lift over

dbSNP: rs41264475; hg19: chr1-159277689; COSMIC: COSV63667451;