19-7698362-G-A

Variant names:

• chr19-7698362-G-A
• rs2228137
• NM_001220500.2:c.184C>T

Variant summary

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

The NM_001220500.2(FCER2):​c.184C>T​(p.Arg62Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,608,806 control chromosomes in the GnomAD database, including 20,203 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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. R62Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.18 (3149 hom., cov: 31)
  • Exomes 𝑓: 0.14 (17054 hom.)
• Consequence: FCER2 NM_001220500.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 41 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0065580606).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001220500.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCER2	NM_001220500.2	MANE Select	c.184C>T	p.Arg62Trp	missense	Exon 4 of 11	NP_001207429.1
	FCER2	NM_002002.5		c.184C>T	p.Arg62Trp	missense	Exon 4 of 11	NP_001993.2
	FCER2	NM_001207019.3		c.181C>T	p.Arg61Trp	missense	Exon 3 of 10	NP_001193948.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCER2	ENST00000597921.6	TSL:1 MANE Select	c.184C>T	p.Arg62Trp	missense	Exon 4 of 11	ENSP00000471974.1
	FCER2	ENST00000346664.9	TSL:1	c.184C>T	p.Arg62Trp	missense	Exon 4 of 11	ENSP00000264072.6
	FCER2	ENST00000360067.8	TSL:5	c.181C>T	p.Arg61Trp	missense	Exon 3 of 10	ENSP00000353178.4

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27945 AN: 151854 Hom.: 3145 Cov.: 31

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0722

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.171

GnomAD2 exomes AF: 0.152 AC: 37873 AN: 249346 AF XY: 0.156

Gnomad AFR exome AF: 0.315

Gnomad AMR exome AF: 0.0795

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.0800

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.142

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.145 AC: 211144 AN: 1456834 Hom.: 17054 Cov.: 30 AF XY: 0.148 AC XY: 107160 AN XY: 724732

African (AFR) AF: 0.319 AC: 10641 AN: 33340

American (AMR) AF: 0.0845 AC: 3760 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 4059 AN: 25990

East Asian (EAS) AF: 0.0551 AC: 2186 AN: 39680

South Asian (SAS) AF: 0.245 AC: 21060 AN: 85828

European-Finnish (FIN) AF: 0.116 AC: 6178 AN: 53352

Middle Eastern (MID) AF: 0.250 AC: 1440 AN: 5752

European-Non Finnish (NFE) AF: 0.138 AC: 152445 AN: 1108224

Other (OTH) AF: 0.156 AC: 9375 AN: 60158

GnomAD4 genome AF: 0.184 AC: 27984 AN: 151972 Hom.: 3149 Cov.: 31 AF XY: 0.183 AC XY: 13605 AN XY: 74282

African (AFR) AF: 0.308 AC: 12761 AN: 41420

American (AMR) AF: 0.126 AC: 1923 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 539 AN: 3466

East Asian (EAS) AF: 0.0724 AC: 374 AN: 5168

South Asian (SAS) AF: 0.251 AC: 1207 AN: 4818

European-Finnish (FIN) AF: 0.124 AC: 1310 AN: 10586

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9381 AN: 67948

Other (OTH) AF: 0.170 AC: 356 AN: 2098

Alfa AF: 0.148 Hom.: 8992

Bravo AF: 0.185

TwinsUK AF: 0.154 AC: 572

ALSPAC AF: 0.146 AC: 562

ESP6500AA AF: 0.300 AC: 1324

ESP6500EA AF: 0.141 AC: 1214

ExAC AF: 0.161 AC: 19599

EpiCase AF: 0.140

EpiControl AF: 0.143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0066	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.5
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.10
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.019	D
Polyphen		0.97	D
Vest4		0.11
MPC		0.082
ClinPred		0.014	T
GERP RS		3.2
Varity_R		0.091
gMVP		0.24
Mutation Taster		=99/1	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: rs2228137; hg19: chr19-7763248; COSMIC: COSV60916093;