rs2251746

Variant names:

• chr1-159302270-T-C
• rs2251746
• ENST00000368115.5:c.-59-36T>C

Variant summary

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

The ENST00000368115.5(FCER1A):​c.-59-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 869,292 control chromosomes in the GnomAD database, including 27,560 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 0.20 (3790 hom., cov: 32)
  • Exomes 𝑓: 0.25 (23770 hom.)
• Consequence: FCER1A ENST00000368115.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606
• Publications: 90 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER1A	NM_002001.4	c.-59-36T>C		intron_variant	Intron 2 of 6		NP_001992.1
FCER1A	NM_001387280.1	c.-95T>C		upstream_gene_variant		ENST00000693622.1	NP_001374209.1
FCER1A	NM_001387282.1	c.-95T>C		upstream_gene_variant			NP_001374211.1
FCER1A	NM_001387281.1	c.-95T>C		upstream_gene_variant			NP_001374210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCER1A	ENST00000368115.5	c.-59-36T>C		intron_variant	Intron 1 of 5	1		ENSP00000357097.1
FCER1A	ENST00000693622.1	c.-95T>C		upstream_gene_variant			NM_001387280.1	ENSP00000509626.1
FCER1A	ENST00000368114.1	c.-95T>C		upstream_gene_variant		3		ENSP00000357096.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30568 AN: 152080 Hom.: 3790 Cov.: 32

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0470

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.208

GnomAD4 exome AF: 0.245 AC: 175782 AN: 717094 Hom.: 23770 Cov.: 9 AF XY: 0.247 AC XY: 94477 AN XY: 382080

African (AFR) AF: 0.0866 AC: 1654 AN: 19092

American (AMR) AF: 0.118 AC: 4982 AN: 42152

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 3172 AN: 20756

East Asian (EAS) AF: 0.0527 AC: 1908 AN: 36186

South Asian (SAS) AF: 0.255 AC: 17621 AN: 68974

European-Finnish (FIN) AF: 0.287 AC: 14911 AN: 51908

Middle Eastern (MID) AF: 0.183 AC: 780 AN: 4256

European-Non Finnish (NFE) AF: 0.280 AC: 122564 AN: 438202

Other (OTH) AF: 0.230 AC: 8190 AN: 35568

GnomAD4 genome AF: 0.201 AC: 30566 AN: 152198 Hom.: 3790 Cov.: 32 AF XY: 0.199 AC XY: 14836 AN XY: 74416

African (AFR) AF: 0.0859 AC: 3570 AN: 41566

American (AMR) AF: 0.167 AC: 2560 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 516 AN: 3472

East Asian (EAS) AF: 0.0469 AC: 243 AN: 5182

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4822

European-Finnish (FIN) AF: 0.279 AC: 2950 AN: 10576

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.278 AC: 18922 AN: 67976

Other (OTH) AF: 0.206 AC: 435 AN: 2112

Alfa AF: 0.248 Hom.: 19269

Bravo AF: 0.184

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		-0.61
PromoterAI		0.15	Neutral
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: rs2251746; hg19: chr1-159272060; COSMIC: COSV63667288; COSMIC: COSV63667288;