Genetic Variant NM_001244753.2:c.498T>C (chr1-161626224-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001244753.2(FCGR3B):c.498T>C(p.Asp166Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00384 in 1,557,940 control chromosomes in the GnomAD database, including 497 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 0.018 ( 216 hom., cov: 28)

Exomes 𝑓: 0.0024 ( 281 hom. )

Consequence

FCGR3B
NM_001244753.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.94

Publications

3 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP7

Synonymous conserved (PhyloP=2.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR3B	NM_001244753.2 link	c.498T>C	p.Asp166Asp	synonymous_variant	Exon 4 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.498T>C	p.Asp166Asp	synonymous_variant	Exon 4 of 5		NM_001244753.2	ENSP00000497461.1		A0A3B3ISU3
ENSG00000289768	ENST00000699402.1 link	c.40+4831T>C		intron_variant	Intron 1 of 3			ENSP00000514363.1		A0A8V8TN80

Frequencies

GnomAD3 genomes

AF:

0.0181

AC:

2676

AN:

147846

Hom.:

216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0636

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00442

Gnomad ASJ

AF:

0.000294

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000647

Gnomad FIN

AF:

0.000195

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000451

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00484

AC:

1196

AN:

247204

AF XY:

0.00356

show subpopulations

Gnomad AFR exome

AF:

0.0651

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.000383

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.000314

Gnomad OTH exome

AF:

0.00200

GnomAD4 exome

AF:

0.00235

AC:

3314

AN:

1409978

Hom.:

281

Cov.:

AF XY:

0.00208

AC XY:

1460

AN XY:

702606

show subpopulations

African (AFR)

AF:

0.0690

AC:

2247

AN:

32572

American (AMR)

AF:

0.00274

AC:

121

AN:

44188

Ashkenazi Jewish (ASJ)

AF:

0.0000393

AC:

AN:

25472

East Asian (EAS)

AF:

0.000405

AC:

AN:

39494

South Asian (SAS)

AF:

0.000855

AC:

AN:

84200

European-Finnish (FIN)

AF:

0.000132

AC:

AN:

52914

Middle Eastern (MID)

AF:

0.00330

AC:

AN:

5448

European-Non Finnish (NFE)

AF:

0.000562

AC:

600

AN:

1067260

Other (OTH)

AF:

0.00397

AC:

232

AN:

58430

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.414

Heterozygous variant carriers

114

228

341

455

569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<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:

0.0181

AC:

2673

AN:

147962

Hom.:

216

Cov.:

AF XY:

0.0171

AC XY:

1234

AN XY:

72262

show subpopulations

African (AFR)

AF:

0.0633

AC:

2540

AN:

40116

American (AMR)

AF:

0.00442

AC:

AN:

14718

Ashkenazi Jewish (ASJ)

AF:

0.000294

AC:

AN:

3400

East Asian (EAS)

AF:

0.000195

AC:

AN:

5132

South Asian (SAS)

AF:

0.000647

AC:

AN:

4636

European-Finnish (FIN)

AF:

0.000195

AC:

AN:

10246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000451

AC:

AN:

66488

Other (OTH)

AF:

0.0152

AC:

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

198

298

397

496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00752

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

3.9

(source)

DANN

Benign

0.69

PhyloP100

2.9

Mutation Taster

=100/0

polymorphism (auto)

(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