1-159304102-A-G

Position:

• chr1-159304102-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001387280.1(FCER1A):​c.251A>G​(p.Lys84Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,614,048 control chromosomes in the GnomAD database, including 145 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0030 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (125 hom.)
• Consequence: FCER1A NM_001387280.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.88

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022898018).
• BP6: Variant 1-159304102-A-G is Benign according to our data. Variant chr1-159304102-A-G is described in ClinVar as [Benign]. Clinvar id is 780087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCER1A	NM_001387280.1	c.251A>G	p.Lys84Arg	missense_variant	3/5	ENST00000693622.1	NP_001374209.1
FCER1A	NM_002001.4	c.251A>G	p.Lys84Arg	missense_variant	5/7		NP_001992.1
FCER1A	NM_001387282.1	c.152A>G	p.Lys51Arg	missense_variant	3/5		NP_001374211.1
FCER1A	NM_001387281.1	c.76+1228A>G		intron_variant			NP_001374210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCER1A	ENST00000693622.1	c.251A>G	p.Lys84Arg	missense_variant	3/5		NM_001387280.1	ENSP00000509626	P1
FCER1A	ENST00000368115.5	c.251A>G	p.Lys84Arg	missense_variant	4/6	1		ENSP00000357097	P1
FCER1A	ENST00000368114.1	c.152A>G	p.Lys51Arg	missense_variant	3/5	3		ENSP00000357096

Frequencies

GnomAD3 genomes AF: 0.00298 AC: 453 AN: 152188 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0751

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00656 AC: 1646 AN: 250980 Hom.: 80 AF XY: 0.00592 AC XY: 803 AN XY: 135622

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0857

Gnomad SAS exome AF: 0.00121

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00174 AC: 2543 AN: 1461742 Hom.: 125 Cov.: 31 AF XY: 0.00165 AC XY: 1203 AN XY: 727176

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0484

Gnomad4 SAS exome AF: 0.00112

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.00810

GnomAD4 genome AF: 0.00296 AC: 451 AN: 152306 Hom.: 20 Cov.: 32 AF XY: 0.00310 AC XY: 231 AN XY: 74476

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0749

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00243 Hom.: 18

Bravo AF: 0.00300

ExAC AF: 0.00596 AC: 724

Asia WGS AF: 0.0310 AC: 108 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	Jul 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0010
DANN	Benign	0.20
DEOGEN2	Benign	0.087	T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.15	T;T
MetaRNN	Benign	0.0023	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.14	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.16	N;N
REVEL	Benign	0.019
Sift	Benign	0.99	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.0	B;.
Vest4		0.032
MVP		0.23
MPC		0.022
ClinPred		0.014	T
GERP RS		-7.4
Varity_R		0.059
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2298804; hg19: chr1-159273892; COSMIC: COSV100929247;