Variant 1-161630018-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001244753.2(FCGR3B):c.79G>C(p.Val27Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,408,556 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000042 ( 1 hom., cov: 17)

Exomes 𝑓: 0.00011 ( 24 hom. )

Consequence

FCGR3B
NM_001244753.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0130

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15233877).

BS2

High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR3B	NM_001244753.2 linkuse as main transcript	c.79G>C	p.Val27Leu	missense_variant	3/5	ENST00000650385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR3B	ENST00000650385.1 linkuse as main transcript	c.79G>C	p.Val27Leu	missense_variant	3/5		NM_001244753.2	P2

Frequencies

GnomAD3 genomes

AF:

0.0000421

AC:

AN:

118744

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:

0.0000861

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000800

AC:

AN:

212538

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

115488

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000169

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000105

AC:

136

AN:

1289812

Hom.:

Cov.:

AF XY:

0.0000748

AC XY:

AN XY:

641668

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000134

Gnomad4 OTH exome

AF:

0.0000189

GnomAD4 genome

AF:

0.0000421

AC:

AN:

118744

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

57148

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000861

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000103

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2021

The c.79G>C (p.V27L) alteration is located in exon 4 (coding exon 3) of the FCGR3B gene. This alteration results from a G to C substitution at nucleotide position 79, causing the valine (V) at amino acid position 27 to be replaced by a leucine (L). 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

Benign

0.18

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.60

Cadd

Benign

Dann

Uncertain

0.97

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.048

M_CAP

Benign

0.0027

MetaRNN

Benign

0.15

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

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

D;D;D;D;D;N;N;N

PrimateAI

Uncertain

0.52

Vest4

0.23, 0.20, 0.20, 0.24, 0.30

MutPred

0.56

Loss of methylation at K25 (P = 0.0725);Loss of methylation at K25 (P = 0.0725);.;.;Loss of methylation at K25 (P = 0.0725);.;.;

MVP

0.18

MPC

0.011

ClinPred

0.054

GERP RS

-0.45

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over