rs148627411

Variant names:

• chr19-7690235-C-G
• rs148627411
• NM_001220500.2:c.652G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-7690235-C-G
• chr19-7690235-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001220500.2(FCER2):​c.652G>C​(p.Gly218Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G218S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FCER2 NM_001220500.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23246676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCER2	NM_001220500.2	c.652G>C	p.Gly218Arg	missense_variant	Exon 10 of 11	ENST00000597921.6	NP_001207429.1
FCER2	NM_002002.5	c.652G>C	p.Gly218Arg	missense_variant	Exon 10 of 11		NP_001993.2
FCER2	NM_001207019.3	c.649G>C	p.Gly217Arg	missense_variant	Exon 9 of 10		NP_001193948.2
FCER2	XM_005272462.5	c.652G>C	p.Gly218Arg	missense_variant	Exon 10 of 11		XP_005272519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCER2	ENST00000597921.6	c.652G>C	p.Gly218Arg	missense_variant	Exon 10 of 11	1	NM_001220500.2	ENSP00000471974.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251364 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461734 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727180

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111898

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.80
DEOGEN2	Benign	0.17	.;T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.75	T;.;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.43	.;N;N
PhyloP100		-0.31
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-4.9	D;D;.
REVEL	Benign	0.040
Sift	Benign	0.050	D;T;.
Sift4G	Benign	0.12	T;T;T
Polyphen		0.84	.;P;P
Vest4		0.12
MutPred		0.56		.;Gain of MoRF binding (P = 0.0395);Gain of MoRF binding (P = 0.0395);
MVP		0.40
MPC		0.28
ClinPred		0.50	D
GERP RS		1.3
Varity_R		0.48
gMVP		0.55
Mutation Taster		=84/16	polymorphism

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: rs148627411; hg19: chr19-7755121;