chr1-159304102-A-G

Variant names:

• chr1-159304102-A-G
• rs2298804
• NM_001387280.1:c.251A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002001.4(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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (125 hom.)
• Consequence: FCER1A NM_002001.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.88
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002001.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCER1A	NM_001387280.1	MANE Select	c.251A>G	p.Lys84Arg	missense	Exon 3 of 5	NP_001374209.1
	FCER1A	NM_002001.4		c.251A>G	p.Lys84Arg	missense	Exon 5 of 7	NP_001992.1
	FCER1A	NM_001387282.1		c.152A>G	p.Lys51Arg	missense	Exon 3 of 5	NP_001374211.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCER1A	ENST00000693622.1	MANE Select	c.251A>G	p.Lys84Arg	missense	Exon 3 of 5	ENSP00000509626.1
	FCER1A	ENST00000368115.5	TSL:1	c.251A>G	p.Lys84Arg	missense	Exon 4 of 6	ENSP00000357097.1
	FCER1A	ENST00000368114.1	TSL:3	c.152A>G	p.Lys51Arg	missense	Exon 3 of 5	ENSP00000357096.1

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

GnomAD2 exomes AF: 0.00656 AC: 1646 AN: 250980 AF XY: 0.00592

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 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

African (AFR) AF: 0.000119 AC: 4 AN: 33478

American (AMR) AF: 0.000201 AC: 9 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0484 AC: 1920 AN: 39686

South Asian (SAS) AF: 0.00112 AC: 97 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111892

Other (OTH) AF: 0.00810 AC: 489 AN: 60386

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

African (AFR) AF: 0.0000481 AC: 2 AN: 41562

American (AMR) AF: 0.00176 AC: 27 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0749 AC: 388 AN: 5182

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00212 Hom.: 21

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.14	N
PhyloP100		-5.9
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.019
Sift	Benign	0.99	T
Sift4G	Benign	0.58	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
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2298804; hg19: chr1-159273892; COSMIC: COSV100929247;