chr1-161629848-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001244753.2(FCGR3B):c.249C>G(p.Asp83Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,426,558 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 6 hom., cov: 10)

Exomes 𝑓: 0.000030 ( 4 hom. )

Consequence

FCGR3B
NM_001244753.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.43

Publications

2 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022362798).

BS2

High Homozygotes in GnomAd4 at 6 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR3B	NM_001244753.2 link	c.249C>G	p.Asp83Glu	missense_variant	Exon 3 of 5	ENST00000650385.1	NP_001231682.2	O75015

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR3B	ENST00000650385.1 link	c.249C>G	p.Asp83Glu	missense_variant	Exon 3 of 5		NM_001244753.2	ENSP00000497461.1		A0A3B3ISU3
ENSG00000289768	ENST00000699402.1 link	c.40+1207C>G		intron_variant	Intron 1 of 3			ENSP00000514363.1		A0A8V8TN80

Frequencies

GnomAD3 genomes

AF:

0.000459

AC:

AN:

78446

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000335

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:

0.0000470

Gnomad OTH

AF:

0.00198

GnomAD2 exomes

AF:

0.000101

AC:

AN:

227300

AF XY:

0.0000567

show subpopulations

Gnomad AFR exome

AF:

0.00109

Gnomad AMR exome

AF:

0.000164

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000942

Gnomad OTH exome

AF:

0.000350

GnomAD4 exome

AF:

0.0000304

AC:

AN:

1348056

Hom.:

Cov.:

AF XY:

0.0000328

AC XY:

AN XY:

671404

show subpopulations

African (AFR)

AF:

0.000976

AC:

AN:

27658

American (AMR)

AF:

0.000171

AC:

AN:

40878

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24918

East Asian (EAS)

AF:

0.00

AC:

AN:

30642

South Asian (SAS)

AF:

0.00

AC:

AN:

77294

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47832

Middle Eastern (MID)

AF:

0.000381

AC:

AN:

5254

European-Non Finnish (NFE)

AF:

9.63e-7

AC:

AN:

1038724

Other (OTH)

AF:

0.0000729

AC:

AN:

54856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.664

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:

0.000459

AC:

AN:

78502

Hom.:

Cov.:

AF XY:

0.000434

AC XY:

AN XY:

36894

show subpopulations

African (AFR)

AF:

0.00169

AC:

AN:

17752

American (AMR)

AF:

0.000335

AC:

AN:

5972

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2486

East Asian (EAS)

AF:

0.00

AC:

AN:

1688

South Asian (SAS)

AF:

0.00

AC:

AN:

1676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4702

Middle Eastern (MID)

AF:

0.00

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.0000470

AC:

AN:

42550

Other (OTH)

AF:

0.00195

AC:

AN:

1024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000337

Hom.:

ESP6500AA

AF:

0.000237

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000921

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 27, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.249C>G (p.D83E) alteration is located in exon 4 (coding exon 3) of the FCGR3B gene. This alteration results from a C to G substitution at nucleotide position 249, causing the aspartic acid (D) at amino acid position 83 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.13

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

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.92

.;.;D;T;D;D;T

MetaRNN

Benign

0.022

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

MetaSVM

Benign

-0.98

PhyloP100

1.4

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.9

.;D;.;.;D;D;D

REVEL

Benign

0.081

Sift

Uncertain

0.0010

.;D;.;.;D;D;D

Sift4G

Uncertain

0.0050

.;D;D;T;D;D;.

Vest4

0.40, 0.40, 0.41, 0.41, 0.44

MutPred

0.58

Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);.;.;Gain of loop (P = 0.1069);.;.;

MVP

0.35

MPC

2.0

ClinPred

0.068

GERP RS

1.9

gMVP

0.47

Mutation Taster

=89/11

polymorphism

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over