rs2277993

Positions:

• chr19-7690685-G-A
• chr19-7690685-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.470-128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 871,008 control chromosomes in the GnomAD database, including 38,400 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 0.35 (10423 hom., cov: 32)
  • Exomes 𝑓: 0.27 (27977 hom.)
• Consequence: FCER2 NM_001220500.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCER2	NM_001220500.2	c.470-128C>T		intron_variant		ENST00000597921.6
FCER2	NM_001207019.3	c.467-128C>T		intron_variant
FCER2	NM_002002.5	c.470-128C>T		intron_variant
FCER2	XM_005272462.5	c.470-128C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCER2	ENST00000597921.6	c.470-128C>T		intron_variant		1	NM_001220500.2	P2

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53061 AN: 151740 Hom.: 10402 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.270 AC: 194033 AN: 719150 Hom.: 27977 AF XY: 0.275 AC XY: 101130 AN XY: 367470

Gnomad4 AFR exome AF: 0.522

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.319

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.299

GnomAD4 genome AF: 0.350 AC: 53112 AN: 151858 Hom.: 10423 Cov.: 32 AF XY: 0.346 AC XY: 25698 AN XY: 74202

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.344

Alfa AF: 0.161 Hom.: 301

Bravo AF: 0.356

Asia WGS AF: 0.346 AC: 1200 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	2.4
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs2277993; hg19: chr19-7755571;