Genetic Variant FCGR3B:p.Ala78Asp (chr1-161629864-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001244753.2(FCGR3B):c.233C>A(p.Ala78Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 1,486,942 control chromosomes in the GnomAD database, including 4,465 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.075 ( 1102 hom., cov: 10)

Exomes 𝑓: 0.028 ( 3363 hom. )

Consequence

FCGR3B
NM_001244753.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.01

Publications

27 publications found

Variant links:

Genes affected

FCGR3B (HGNC:3620): (Fc gamma receptor IIIb) The protein encoded by this gene is a low affinity receptor for the Fc region of gamma immunoglobulins (IgG). The encoded protein acts as a monomer and can bind either monomeric or aggregated IgG. This gene may function to capture immune complexes in the peripheral circulation. Several transcript variants encoding different isoforms have been found for this gene. A highly-similar gene encoding a related protein is also found on chromosome 1. [provided by RefSeq, Aug 2012]

FCGR3B Gene-Disease associations (from GenCC):

systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

FCGR3B links:

ENSG00000289768 (HGNC:):

ENSG00000289768 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0067406297).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR3B	NM_001244753.2 link	c.233C>A	p.Ala78Asp	missense_variant	Exon 3 of 5	ENST00000650385.1	NP_001231682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR3B	ENST00000650385.1 link	c.233C>A	p.Ala78Asp	missense_variant	Exon 3 of 5		NM_001244753.2	ENSP00000497461.1
ENSG00000289768	ENST00000699402.1 link	c.40+1191C>A		intron_variant	Intron 1 of 3			ENSP00000514363.1

Frequencies

GnomAD3 genomes

AF:

0.0748

AC:

6124

AN:

81818

Hom.:

1102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.0490

Gnomad AMR

AF:

0.0386

Gnomad ASJ

AF:

0.0218

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0344

Gnomad MID

AF:

0.0482

Gnomad NFE

AF:

0.0292

Gnomad OTH

AF:

0.0589

GnomAD2 exomes

AF:

0.0378

AC:

9301

AN:

245862

AF XY:

0.0374

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.0194

Gnomad ASJ exome

AF:

0.0238

Gnomad EAS exome

AF:

0.000170

Gnomad FIN exome

AF:

0.0261

Gnomad NFE exome

AF:

0.0216

Gnomad OTH exome

AF:

0.0313

GnomAD4 exome

AF:

0.0279

AC:

39227

AN:

1405084

Hom.:

3363

Cov.:

AF XY:

0.0294

AC XY:

20540

AN XY:

697870

show subpopulations

African (AFR)

AF:

0.207

AC:

6172

AN:

29748

American (AMR)

AF:

0.0214

AC:

902

AN:

42126

Ashkenazi Jewish (ASJ)

AF:

0.0241

AC:

608

AN:

25194

East Asian (EAS)

AF:

0.0000317

AC:

AN:

31540

South Asian (SAS)

AF:

0.0847

AC:

6843

AN:

80818

European-Finnish (FIN)

AF:

0.0258

AC:

1278

AN:

49464

Middle Eastern (MID)

AF:

0.0342

AC:

186

AN:

5440

European-Non Finnish (NFE)

AF:

0.0197

AC:

21304

AN:

1083652

Other (OTH)

AF:

0.0339

AC:

1933

AN:

57102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1133

2267

3400

4534

5667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.0749

AC:

6131

AN:

81858

Hom.:

1102

Cov.:

AF XY:

0.0762

AC XY:

2931

AN XY:

38460

show subpopulations

African (AFR)

AF:

0.228

AC:

4039

AN:

17684

American (AMR)

AF:

0.0386

AC:

247

AN:

6402

Ashkenazi Jewish (ASJ)

AF:

0.0218

AC:

AN:

2574

East Asian (EAS)

AF:

0.00

AC:

AN:

1874

South Asian (SAS)

AF:

0.120

AC:

216

AN:

1804

European-Finnish (FIN)

AF:

0.0344

AC:

173

AN:

5032

Middle Eastern (MID)

AF:

0.0467

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.0291

AC:

1303

AN:

44702

Other (OTH)

AF:

0.0582

AC:

AN:

1082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

136

272

407

543

679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0228

Hom.:

185

ESP6500AA

AF:

0.194

AC:

839

ESP6500EA

AF:

0.0199

AC:

171

ExAC

AF:

0.0418

AC:

5053

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.019

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.0

.;.;T;.;.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

LIST_S2

Benign

0.0

.;.;T;T;T;T;T

MetaRNN

Benign

0.0067

T;T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

.;.;.;.;.;.;.

PhyloP100

-2.0

PrimateAI

Benign

0.31

PROVEAN

Benign

0.0

.;N;.;.;N;N;N

Sift

Pathogenic

0.0

.;T;.;.;T;T;T

Sift4G

Pathogenic

0.0

.;T;T;T;T;T;.

Vest4

0.0

ClinPred

0.00048

GERP RS

-4.0

gMVP

0.20

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over