rs540459343

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001244753.2(FCGR3B):​c.649C>T​(p.Leu217Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,457,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L217V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

FCGR3B
NM_001244753.2 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.254
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14793059).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FCGR3BNM_001244753.2 linkc.649C>T p.Leu217Phe missense_variant Exon 5 of 5 ENST00000650385.1 NP_001231682.2 O75015

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FCGR3BENST00000650385.1 linkc.649C>T p.Leu217Phe missense_variant Exon 5 of 5 NM_001244753.2 ENSP00000497461.1 A0A3B3ISU3
ENSG00000289768ENST00000699402.1 linkc.40+6487C>T intron_variant Intron 1 of 3 ENSP00000514363.1 A0A8V8TN80

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250258
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135272
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1457202
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
724936
show subpopulations
Gnomad4 AFR exome
AF:
0.0000605
Gnomad4 AMR exome
AF:
0.0000224
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:
9.02e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
14
DANN
Benign
0.94
DEOGEN2
Benign
0.034
.;.;T;.;.;.
Eigen
Benign
-0.97
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.063
N
LIST_S2
Benign
0.66
.;.;T;T;T;T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.15
T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
PrimateAI
Benign
0.35
T
PROVEAN
Uncertain
-2.6
.;D;.;.;D;D
REVEL
Benign
0.15
Sift
Benign
0.059
.;T;.;.;T;T
Sift4G
Benign
0.14
.;T;T;T;T;T
Vest4
0.10, 0.089, 0.077, 0.10, 0.23
MVP
0.081
MPC
0.18
ClinPred
0.030
T
GERP RS
-3.0
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.20
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.20
Position offset: -13

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.

Other links and lift over

dbSNP: rs540459343; hg19: chr1-161594358; API