Genetic Variant FCER2:c.470-26A>G (chr19-7690583-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001220500.2(FCER2):c.470-26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,603,798 control chromosomes in the GnomAD database, including 72,819 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.35 ( 10335 hom., cov: 32)

Exomes 𝑓: 0.29 ( 62484 hom. )

Consequence

FCER2
NM_001220500.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.04

Publications

4 publications found

Variant links:

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]

FCER2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001220500.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FCER2	NM_001220500.2	MANE Select	c.470-26A>G	intron	N/A	NP_001207429.1	P06734
FCER2	NM_002002.5		c.470-26A>G	intron	N/A	NP_001993.2
FCER2	NM_001207019.3		c.467-26A>G	intron	N/A	NP_001193948.2	K3W4U1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FCER2	ENST00000597921.6	TSL:1 MANE Select	c.470-26A>G	intron	N/A	ENSP00000471974.1	P06734
FCER2	ENST00000346664.9	TSL:1	c.470-26A>G	intron	N/A	ENSP00000264072.6	P06734
FCER2	ENST00000360067.8	TSL:5	c.467-26A>G	intron	N/A	ENSP00000353178.4	K3W4U1

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

52891

AN:

151530

Hom.:

10314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.527

Gnomad AMI

AF:

0.347

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.343

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.349

GnomAD2 exomes

AF:

0.294

AC:

70971

AN:

241500

AF XY:

0.298

show subpopulations

Gnomad AFR exome

AF:

0.532

Gnomad AMR exome

AF:

0.160

Gnomad ASJ exome

AF:

0.319

Gnomad EAS exome

AF:

0.365

Gnomad FIN exome

AF:

0.227

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.281

GnomAD4 exome

AF:

0.288

AC:

417523

AN:

1452150

Hom.:

62484

Cov.:

AF XY:

0.290

AC XY:

209514

AN XY:

722120

show subpopulations

African (AFR)

AF:

0.546

AC:

18196

AN:

33340

American (AMR)

AF:

0.170

AC:

7516

AN:

44180

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

8307

AN:

25856

East Asian (EAS)

AF:

0.294

AC:

11633

AN:

39542

South Asian (SAS)

AF:

0.363

AC:

31106

AN:

85578

European-Finnish (FIN)

AF:

0.227

AC:

11630

AN:

51180

Middle Eastern (MID)

AF:

0.385

AC:

2191

AN:

5688

European-Non Finnish (NFE)

AF:

0.279

AC:

308358

AN:

1106776

Other (OTH)

AF:

0.310

AC:

18586

AN:

60010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

13338

26677

40015

53354

66692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10464

20928

31392

41856

52320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.349

AC:

52942

AN:

151648

Hom.:

10335

Cov.:

AF XY:

0.346

AC XY:

25625

AN XY:

74110

show subpopulations

African (AFR)

AF:

0.528

AC:

21797

AN:

41310

American (AMR)

AF:

0.254

AC:

3882

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

1101

AN:

3466

East Asian (EAS)

AF:

0.344

AC:

1762

AN:

5126

South Asian (SAS)

AF:

0.378

AC:

1816

AN:

4810

European-Finnish (FIN)

AF:

0.228

AC:

2400

AN:

10536

Middle Eastern (MID)

AF:

0.373

AC:

109

AN:

292

European-Non Finnish (NFE)

AF:

0.281

AC:

19035

AN:

67828

Other (OTH)

AF:

0.344

AC:

726

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1653

3306

4960

6613

8266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.325

Hom.:

1503

Bravo

AF:

0.356

Asia WGS

AF:

0.346

AC:

1200

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.89

(source)

DANN

Benign

0.44

PhyloP100

-3.0

BranchPoint Hunter

0.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over