dbSNP rs200688856: FCGR3B:p.Ser36Ser (chr1-161629989-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2

The NM_001244753.2(FCGR3B):c.108C>T(p.Ser36Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,363,282 control chromosomes in the GnomAD database, including 10 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.

Frequency

Genomes: 𝑓 0.000046 ( 1 hom., cov: 17)

Exomes 𝑓: 0.000026 ( 9 hom. )

Consequence

FCGR3B
NM_001244753.2 synonymous

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: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.045).

BP7

Synonymous conserved (PhyloP=-1.01 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 9 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR3B	NM_001244753.2 link	c.108C>T	p.Ser36Ser	synonymous_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>T	p.Ser36Ser	synonymous_variant	Exon 3 of 5		NM_001244753.2	ENSP00000497461.1
ENSG00000289768	ENST00000699402.1 link	c.40+1066C>T		intron_variant	Intron 1 of 3			ENSP00000514363.1

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

108250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000940

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000432

AC:

AN:

208406

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000500

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000263

AC:

AN:

1255032

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

623504

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

25938

American (AMR)

AF:

0.00

AC:

AN:

34302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23846

East Asian (EAS)

AF:

0.00

AC:

AN:

24980

South Asian (SAS)

AF:

0.0000735

AC:

AN:

68040

European-Finnish (FIN)

AF:

0.0000220

AC:

AN:

45538

Middle Eastern (MID)

AF:

0.000199

AC:

AN:

5022

European-Non Finnish (NFE)

AF:

0.0000246

AC:

AN:

976126

Other (OTH)

AF:

0.0000390

AC:

AN:

51240

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000302712), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.398

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

<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:

0.0000462

AC:

AN:

108250

Hom.:

Cov.:

AF XY:

0.0000383

AC XY:

AN XY:

52158

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27146

American (AMR)

AF:

0.00

AC:

AN:

9612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2922

East Asian (EAS)

AF:

0.00

AC:

AN:

2420

South Asian (SAS)

AF:

0.00

AC:

AN:

2836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7808

Middle Eastern (MID)

AF:

0.00

AC:

AN:

248

European-Non Finnish (NFE)

AF:

0.0000940

AC:

AN:

53186

Other (OTH)

AF:

0.00

AC:

AN:

1468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

5.1

(source)

DANN

Benign

0.82

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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