Genetic Variant FCGR3B:p.Ser36Arg (chr1-161629989-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001244753.2(FCGR3B):c.108C>G(p.Ser36Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.00071 ( 1 hom., cov: 17)

Exomes 𝑓: 0.0039 ( 2339 hom. )

Failed GnomAD Quality Control

Consequence

FCGR3B
NM_001244753.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.01

Publications

21 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0085681975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR3B	NM_001244753.2 link	c.108C>G	p.Ser36Arg	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.108C>G	p.Ser36Arg	missense_variant	Exon 3 of 5		NM_001244753.2	ENSP00000497461.1
ENSG00000289768	ENST00000699402.1 link	c.40+1066C>G		intron_variant	Intron 1 of 3			ENSP00000514363.1

Frequencies

GnomAD3 genomes

AF:

0.000715

AC:

AN:

107672

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000518

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000943

Gnomad ASJ

AF:

0.000345

Gnomad EAS

AF:

0.00253

Gnomad SAS

AF:

0.00142

Gnomad FIN

AF:

0.000128

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000775

Gnomad OTH

AF:

0.000686

GnomAD2 exomes

AF:

0.0115

AC:

2393

AN:

208406

AF XY:

0.0114

show subpopulations

Gnomad AFR exome

AF:

0.0137

Gnomad AMR exome

AF:

0.0156

Gnomad ASJ exome

AF:

0.00311

Gnomad EAS exome

AF:

0.0566

Gnomad FIN exome

AF:

0.00140

Gnomad NFE exome

AF:

0.00672

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00388

AC:

4861

AN:

1252378

Hom.:

2339

Cov.:

AF XY:

0.00434

AC XY:

2701

AN XY:

622174

show subpopulations

African (AFR)

AF:

0.00552

AC:

143

AN:

25888

American (AMR)

AF:

0.0155

AC:

530

AN:

34116

Ashkenazi Jewish (ASJ)

AF:

0.00206

AC:

AN:

23778

East Asian (EAS)

AF:

0.0271

AC:

670

AN:

24680

South Asian (SAS)

AF:

0.0152

AC:

1033

AN:

67886

European-Finnish (FIN)

AF:

0.00220

AC:

100

AN:

45438

Middle Eastern (MID)

AF:

0.00299

AC:

AN:

5014

European-Non Finnish (NFE)

AF:

0.00216

AC:

2101

AN:

974504

Other (OTH)

AF:

0.00431

AC:

220

AN:

51074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.556

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000715

AC:

AN:

107726

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

51976

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000516

AC:

AN:

27112

American (AMR)

AF:

0.000943

AC:

AN:

9544

Ashkenazi Jewish (ASJ)

AF:

0.000345

AC:

AN:

2902

East Asian (EAS)

AF:

0.00253

AC:

AN:

2370

South Asian (SAS)

AF:

0.00143

AC:

AN:

2798

European-Finnish (FIN)

AF:

0.000128

AC:

AN:

7788

Middle Eastern (MID)

AF:

0.00

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.000775

AC:

AN:

52914

Other (OTH)

AF:

0.000681

AC:

AN:

1468

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.249

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0145

Hom.:

ExAC

AF:

0.000386

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.23

(source)

DANN

Benign

0.43

DEOGEN2

Benign

0.0

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

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00075

LIST_S2

Benign

0.0

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

MetaRNN

Benign

0.0086

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

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

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

PhyloP100

-1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

0.0

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

REVEL

Benign

0.0

Sift

Pathogenic

0.0

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

Sift4G

Pathogenic

0.0

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

Vest4

0.0

ClinPred

0.00066

GERP RS

-5.1

gMVP

0.27

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