19-7698362-G-A

Position:

• chr19-7698362-G-A

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 (MetaRNN=0.0065580606).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCER2	NM_001220500.2	c.184C>T	p.Arg62Trp	missense_variant	4/11	ENST00000597921.6	NP_001207429.1
FCER2	NM_002002.5	c.184C>T	p.Arg62Trp	missense_variant	4/11		NP_001993.2
FCER2	NM_001207019.3	c.181C>T	p.Arg61Trp	missense_variant	3/10		NP_001193948.2
FCER2	XM_005272462.5	c.184C>T	p.Arg62Trp	missense_variant	4/11		XP_005272519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCER2	ENST00000597921.6	c.184C>T	p.Arg62Trp	missense_variant	4/11	1	NM_001220500.2	ENSP00000471974	P2

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

GnomAD3 exomes AF: 0.152 AC: 37873 AN: 249346 Hom.: 3516 AF XY: 0.156 AC XY: 21030 AN XY: 134692

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 SAS exome AF: 0.252

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

Gnomad4 AFR exome AF: 0.319

Gnomad4 AMR exome AF: 0.0845

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.0551

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.156

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

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0724

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.170

Alfa AF: 0.142 Hom.: 4328

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 v4.3

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;T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.76	T;.;T;T
MetaRNN	Benign	0.0066	T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.0	.;L;L;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.5	N;N;.;.
REVEL	Benign	0.10
Sift	Uncertain	0.0070	D;D;.;.
Sift4G	Uncertain	0.019	D;D;D;D
Polyphen		0.97	.;D;D;.
Vest4		0.11
MPC		0.082
ClinPred		0.014	T
GERP RS		3.2
Varity_R		0.091
gMVP		0.24

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: rs2228137; hg19: chr19-7763248; COSMIC: COSV60916093;