rs2287867

chr19-7699855-G-Achr19-7699855-G-Cchr19-7699855-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001220500.2(FCER2):c.-85-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 1,221,064 control chromosomes in the GnomAD database, including 179,865 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 0.50 (19861 hom., cov: 31)
  • Exomes 𝑓: 0.55 (160004 hom.)
• Consequence: FCER2 NM_001220500.2 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0003733
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

Genes affected

FCER2 (HGNC:3612): (Fc epsilon receptor II) The protein encoded by this gene is a B-cell specific antigen, and a low-affinity receptor for IgE. It has essential roles in B cell growth and differentiation, and the regulation of IgE production. This protein also exists as a soluble secreted form, then functioning as a potent mitogenic growth factor. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCER2	NM_001220500.2	c.-85-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000597921.6
FCER2	NM_002002.5	c.-85-10C>T		splice_polypyrimidine_tract_variant, intron_variant
FCER2	XM_005272462.5	c.-81-14C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCER2	ENST00000597921.6	c.-85-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001220500.2	P2

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76487 AN: 151880 Hom.: 19835 Cov.: 31

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.546 AC: 583610 AN: 1069066 Hom.: 160004 Cov.: 14 AF XY: 0.548 AC XY: 299545 AN XY: 546256

Gnomad4 AFR exome AF: 0.376

Gnomad4 AMR exome AF: 0.527

Gnomad4 ASJ exome AF: 0.591

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.577

Gnomad4 FIN exome AF: 0.584

Gnomad4 NFE exome AF: 0.540

Gnomad4 OTH exome AF: 0.541

GnomAD4 genome AF: 0.504 AC: 76555 AN: 151998 Hom.: 19861 Cov.: 31 AF XY: 0.507 AC XY: 37681 AN XY: 74282

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.581

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.530

Alfa AF: 0.536 Hom.: 11679

Bravo AF: 0.492

Asia WGS AF: 0.630 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	16
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00037
dbscSNV1_RF	Benign	0.052
SpliceAI score (max)		0.030		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: rs2287867; hg19: chr19-7764741;