rs2494264

Variant names:

• chr1-159297048-T-A
• rs2494264
• ENST00000368115.5:c.-59-5258T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000368115.5(FCER1A):​c.-59-5258T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,074 control chromosomes in the GnomAD database, including 10,773 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (10773 hom., cov: 32)
• Consequence: FCER1A ENST00000368115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.911
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER1A	NM_002001.4	c.-59-5258T>A		intron_variant	Intron 2 of 6		NP_001992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCER1A	ENST00000368115.5	c.-59-5258T>A		intron_variant	Intron 1 of 5	1		ENSP00000357097.1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52034 AN: 151954 Hom.: 10775 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.372

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.342 AC: 52046 AN: 152074 Hom.: 10773 Cov.: 32 AF XY: 0.338 AC XY: 25088 AN XY: 74326

African (AFR) AF: 0.119 AC: 4945 AN: 41500

American (AMR) AF: 0.338 AC: 5159 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1243 AN: 3470

East Asian (EAS) AF: 0.204 AC: 1053 AN: 5170

South Asian (SAS) AF: 0.322 AC: 1550 AN: 4820

European-Finnish (FIN) AF: 0.443 AC: 4678 AN: 10558

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32149 AN: 67970

Other (OTH) AF: 0.370 AC: 783 AN: 2114

Alfa AF: 0.406 Hom.: 1749

Bravo AF: 0.323

Asia WGS AF: 0.218 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.67
PhyloP100		0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2494264; hg19: chr1-159266838; COSMIC: COSV107460921;